comparative genomic hybridization array study and its

Indian Journal of Experimental Biology

Vol. 47, October 2009, pp. 779-791

Review Article

Comparative genomic hybridization array study and its utility in detection of

constitutional and acquired anomalies

Joris Andrieux & Frenny Sheth*

Laboratory of Medical Genetics, Jeanne de Flandre Hospital CHRU de Lille, Lille Cedex, France

The last decade has witnessed an upsurge in the knowledge of cytogenetic disorders and putting the old technology in a

new basket with molecular genetics. As conventional cytogenetic can detect the genetic alteration of 10-15 Mb, many of the

micro-deletions and micro-duplications are missed. However, with the advent of technology of fluorescence in situ

hybridization (FISH), the resolution of genetic aberrations can reach to 3-5 Mb, nonetheless the anomalies smaller than the

above, need further precision which has been achieved using comparative genomic hybridization array (CGH-array).

Introduction of array-CGH has brought higher sensitivity with automated DNA fragment analyzer and DNA chip for

submicroscopic chromosomal anomalies that are missed till date in many of the acquired and constitutional genetic

disorders. The resolution of the technology varies from several Kb to 1 Mb depending upon the type of array selected. With

the recent improvement in the array-CGH technology, a link between cytogenetic and molecular biology has been

established without replacing conventional cytogenetic technique. The wider accessibility of the technology shall certainly

provide a clue to the many unidentified/unexplained genetic disorders which shall prove to be a boon to the clinicians.

Keywords: Acquired anomalies, Array-CGH, Constitutional disorders, Molecular karyotyping

Cytogenetic study has remained the clinicians’

favorite for many of the genetic disorders especially

in unexplained psychomotor retardation [with/without

dysmorphism], abnormality of sexual differentiation

and development, infertility, recurrent pregnancy loss,

pregnancy at risk for aneuploidy, chromosome

breakage syndrome and cancer. However, limitation

of band resolution has added the plethora of research

studies in search for technology that can visualize

chromosomal anomalies which are thought to be not

existing or missed. This has transformed cytogenetics

to the molecular cytogenetics with an unmatched

precision and knowledge gained so far. Though

chromosomal abnormalities remain a major cause of

most of the genetic disorders, limitations of high

resolution, missed many of the genetic disorders

while molecular biology has its limitations of known

targeted anomalies identification. These limitations

have transformed the newer innovation with high end

precision of cytogenetic techniques (Table 1).

Nonetheless all these technology have their limitation

that uses comprehensive analysis of the disorders

Table 1—Landmark in the history of conventional cytogenetic

and molecular cytogenetic

Year Discovery Ref.

1959 First Chromosomal anomaly

detected [Trisomy 21]

Lejune J1

1969 Molecular hybridization of

radioactive DNA to the DNA of

cytological preparations

Pardue & Gall2

1976 High resolution banding

technique

Yunis3

1981 Isotopic in situ hybridization Harper & Saunders4

1984 Direct FISH Landegent5

1986 Interphase FISH Cremer et al6 & Pinkel

et al7

1989 Combinatorial labeling Nederlof et al8

1989 Primed in situ hybridization

[PRINS]

Koch et al9

1990 Identification of translocation in

Interphase cell by FISH

Tkachuk et al10

1990 Technique of ratio labeling Nederlof et al11

1992 Comparative Genomic

Hybridization [CGH]

Kallioniemi et al12

1993 Fiber FISH Parra & Windle13

1996 Multiplex FISH [M-FISH] Speicher et al14

1996 SKY Schrock et al15

1997 Cross species color Banding

[Rx FISH]

Muller et al16

1997 DNA array (matrix) CGH Solinas-Toldo17

1997 Padlock probe FISH Nilsson et al18

1998 Array CGH using BAC clones Pinkel et al19

——————

*Correspondent author’s present address:

FRIGE (Foundation for Research in Genetics and Endocrinology),

Institute of Human Genetics, FRIGE House, Jodhpur Road,

Satellite, Ahmedabad 380 015, India

Telephone: 079-26921414

Fax: 079-26921415

E-mail: [email protected]

INDIAN J EXP BIOL, OCTOBER 2009

780

using cytogenetics to molecular cytogenetics to

array—comparative genomic hybridization (CGH).

Table 2 shows comparison of each technology, its

uses and limitations for understanding genomic

imbalances in various genetic disorders.

Techniques and levels of resolution Conventional cytogenetic [CC] technique, the

standard karyotype (400-bands per haploid genome)

allows a level of resolution, from 10-15 Mb (million

base pairs). In the best conditions, the high-resolution

karyotype (550-bands) allows to reveal anomalies of

about 3 to 5 Mb according to the regions of the

genome and the technique used (G-bands, R-bands).

The limitation of enhance resolution of the karyotype

is not only linked to the cytogenetic technique used (it

is possible to get karyotypes up to 850-bands), but

also the region of interest.

Secondly, the cytogenetic technique is only partly

automated; need insight, indebt knowledge and

experience of the cytogeneticists.

Molecular biology allows precise analysis of

variations at the nucleotide level. Molecular

cytogenetic techniques, mainly Fluorescence in situ

hybridization (FISH), which is currently useful on

both metaphase chromosomes and interphase cells,

utilize genomic sequence-probes in bacterial

artificial chromosome [BAC 100-200 kb] cloned in

Escherichia coli or P1 artificial chromosome [PAC

100-150 kb] cloned in phage. These sequences are

tagged with fluorochrome, which allows the

detection of genomic imbalances involving

chromosome segments smaller than 1 Mb for

deletions and more than 2 Mb for duplications. This

technique is more useful to detect micro-deletion and

alteration at the telomeric region, which are not

identifiable with conventional cytogenetics (CC).

This can be confirmed and correlated with the

clinical symptoms. It is important to know that this

technique can identify only the specific region of the

interest [specific sequence used as probe] and not the

whole genome in a single assay.

Table 2—Comparison of technical details between conventional cytogenetic and major molecular approaches

Method Analysis Resolution Applications Limitation

Conventional

cytogenetics

Cell culturing:

arresting cell in

metaphase

Whole genome 10-15 Mb Detection of balance and unbalance

defects

Minor rearrangements

cannot be detected

High resolution

banding technique

arresting cell in

metaphase

Whole genome 3-5 Mb Detection of balance and unbalance

defects

Micro-deletions and

terminal aberrations can

not be detected.

1-3 Mb

Metaphase

Conventional

FISH

Molecular

biology

technique

Identify

specific region

50 Kb

Interphase cells

Detect all types of balanced and

unbalanced defects in metaphase,

interphase cell, frozen section and

dead cells.

Structural anomalies

cannot be detected in non-

dividing cells. Smaller

FISH is highly sensitive

for trisomy than

monosomy

Spectral

Karyoytping/ M-

FISH

arresting cell in

metaphase

Whole genome 1-2 Mb Detect numerical and structural

aberrations including subtle

rearrangements, complex

translocation, small marker, ring

and double minute chromosomes in

a single experiments with all 24

chromosomes

Inability to detect

paracentromeric inversion,

small deletion/duplications

and cryptic translocation

CGH Molecular

biology technique

Whole genome 3-5 Mb No need for cell culture or

metaphase, does not require fresh

sample, frozen or fixed sample can

be used, interpretation of highly

complex karyotype with accurate

chromosomal location of imbalance

Cannot detect Balanced

translocation, gain/loss of

<4 Mb, multiplication of

2n

Array-CGH Molecular

biology technique

Whole genome 20 - 150 Kb Specifications are same as above.

Can identify cryptic

rearrangements, More sensitive and

can be use for both quantitative

genomic imbalance and gene

expression as well

Cannot detect balanced

translocation, mosaicism

less than 50%, and

heterochromatic region

ANDRIEUX & SHETH : CGH-ARRAY STUDY & ITS UTILITIES

781

Another molecular technique to analyse pange-

nomic alteration is CGH on metaphase. Here test

DNA (patient) and reference DNA (normal

individual) are differentially labeled with two

fluorescence dyes and co-hybridized on metaphase

spreads of a normal individual. A copy number

difference between test DNA and reference DNA will

be reflected in fluorescence ratio. These ratios of

fluorochromes are visualised under microscope using

appropriate filters and analysed with the aid of

software that discern genome structure variation

[deletion, duplication, amplifications, monosomies,

trisomies etc.] present in the DNA of the patient. This

technique has an advantage of identifying anomalies

in segments, which are not identified by G- or R-

banding technique. Secondly, DNA of the test subject

is used for the processing and hybridizes on the

normal male metaphase hence culturing of the cells

are not required. This is mainly useful in cases of

prenatal, onco-hematological and in tumor cases as

well. One of the limits of CGH on chromosomes, in

addition to poor reproducibility is its level of

resolution, which does not exceed 3-5 Mb [similar to

high-resolution banding] (Fig. 1).

Recent advancements in array-CGH has made it

possible to substitute the chromosome target with

DNA spotted on a glass slide. The processing

technique is similar to that of CGH metaphase. Equal

quantities of DNA from the patient and control are

labelled with different fluorochromes and hybridized

on a glass slide coated with an ordered set of defined

nucleic acid sequences17

. This technological

development allows screening of large number of

genomic DNA sequences in a single experiment,

depending on the size of the spotlength of DNA

[60bp]. Chromosomal imbalances across the genome

can be mapped and quantified by analyzing the

fluorescence ratio of the two dyes for each target.

DNA quantitative variation can be identified, only if

the DNA fragments used on the glass slide covers

regions of interest.

Technological progress accomplished in the last

years, allow spotting of more than a million fragments

of DNA. Particularly for pangenomic studies, the

resolution depends on the number of DNA probes

spotted on the coated glass and the resolution is very

close to few kilobases. This has made possible several

applications such as whole chromosome studies20

, a

chromosome segment21

, all sub-telomeric regions22

, or

entire genome with a 1Mb resolution ranging from

(classical BACs/PACs array) to 10-100kb

(oligonucleotide array). Hence, this is going to

provide the “connecting link” between cytogenetic

and molecular biology for quantitative detection of

structural variation at genomic level. The term of

molecular karyotype is now closer to reality23,24

.

Types of CGH-array

BAC/PAC arrays— The use of DNA from cosmid,

P1, BAC and other large insert clones as targets were

first shown by Pinkel et al19

. 1 Mb resolution can be

achieved by using 3200-3500 clones covering the

entire genome. Using this array, many cryptic

polymorphisms have been detected. However, array-

CGH using BACs/PACs create difficulties to

differentiate between potentially pathogenic and poly-

morphisms as around 10% of the used clones are

polymorphic25

. In addition presence of Common

Number Variations / Polymorphisms (CNV/CNP)

further confounds analysis.

Recently overlapping clones [tiling path array

using 32,433 clones]26

have been used which provide

resolution of ~200kb on average. These have higher

cost than the 3200-3500 but allows detection of more

number of variations.

Oligonucleotide array — Commercially available

array-CGH oligonucleotides are available with

densities of clones from 15,000-1 million probes. This

increases the resolution up to 20-30 kb on the entire

Fig. 1—CGH on chromosome (http:// www.sanger.ac.uk/ HGP/

Cytogenetics/)


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genome with an increased density in the coding

region of the genome27

.

Another approach is to use Single Nucleotide

Polymorphisms (SNP) micro-arrays, which allow

detection of partial/complete disomies28

when finding

losses of heterozygosity (LOH) without quantitative

DNA imbalances.

Databases and bio-computer science—Data

processing plays a central role in interpretation.

Various softwares have been developed allowing to

process the data, to facilitate the interpretation using

statistical algorithms and to generate a graph of the

results automatically. Nonetheless the interpretation

of these data is done only after studying whole

genome databases (Ensembl - Cambridge, UK-,

UCSC Genome Browser - Santa Cruz, USA) and

database of polymorphisms (Database of Genomic

Variants, Toronto, Canada) (Fig. 2).

Applications

Applications in onco-hematology and tumors—

From the literature survey it can be noticed that CGH

micro-array was totally used to rule out genetic

alterations in onco-haematological and tumor

pathology until 2005 (Table 3).

In this domain, detection of quantitative genomic

alterations was linked to tumor progression and its

therapeutic approach92

. Various pathologies studied

are shown in Table 3.

Though pathologies are secondary to the

anomalies, it helps not only in the diagnosis but in the

prognosis as well. There is specificity and limitations

linked in CGH-Array applied to cancers and to

leukaemias are as follows:

Clonal anomalies: Different cell population (tumor

and normal) are frequently observed in samples.

Minor clone anomalies can easily be detected by CC

as cell culture allows the immature cells to divide for

the analysis but in array-CGH, the DNA of normal

cells is mixed with DNA from abnormal cell

population. Hence, abnormal clone if less than 30%,

cannot be detected by array-CGH (Fig. 3).

Sample preparation: Especially in solid tumor,

sometimes DNA is extracted from the fixed histo

Fig. 2—Interpretation of the data using whole genome databases


783

pathological tissue that often generates poor quality

DNA leading to improper hybridization and inter-

pretation difficulties.

Patient data: Large number of patients DNA is

required for same clinical diagnosis to identify

recurrent anomalies by array-CGH.

Applications in constitutional abnormalities— In

term of diagnosis, array-CGH is particularly well

suitable for the constitutional anomalies where they

find, more often causative genetic alterations than in

onco-haematology and cancers, where they find

anomalies often consequence to the disease.

• Application of array: CGH in constitutional genetic

is validation and measurement of the abnormality

detected by CC. Array-CGH is very useful to map

and measure precisely the size of the aberration

using region specific arrays. CC analysis showed

additional genetic material on #8p arm to a 3 yrs

old female having MCA and developmental

delay [ 46, XX,add(8) † (8;?)(p23;?)]. Array - CGH

Table 3—Examples of onco-hematology and solid tumors studied

by array-CGH

Diseases Ref.

Acute myeloid leukemia, myelodysplasia 29-34

Acute lymphocytic leukemia 35-41

Chronic myelogenous leukemia 42

Chronic lymphocytic leukemia 43,44

Lymphoma 45-50

Multiple myeloma 51,52

Mesothelioma 53-55

Breast cancer 56-63

Ovary cancer 64,65

Colorectal adenocarcinoma 66-68

Liver cancer 69-71

Pancreatic cancer 72,73

Bladder cancer 74-76

Prostate cancer 77-79

Neuroblastoma 80-83

Glioblastoma 84-86

Medulloblastoma 87,88

Thyroid cancer 89,90

Thymoma 91

Fig. 3–Minor clones [~50%] cannot be detected by array-CGH


784

confirmed deletion of 8.3Mb on #8 and duplication

of 42.2 Mb of #15 leading to partial monosomy of

#8p and partial trisomy of #15q (Fig. 4 a-c). To

date several chromosomal regions or whole

chromosomes were studied using tiling path or

high-resolution array21

.

• To identify de novo marker chromosomes: measure

precisely gain and/or loss of chromosomal

segment, in a single assay (Fig. 5 a-b) 93-96

• In the vast majority of cases, apparently balanced

structural chromosome abnormalities are not

associated with an abnormal phenotype. However,

some carriers of apparently balanced de novo or

inherited rearrangements present abnormal

phenotypic features. The abnormal phenotype may

be explained by the disruption of a gene, a

positional effect or a cryptic genomic imbalance at

the breakpoint or in another region of the genome

as seen in Fig. 4c where duplication of 15q23q26.3

involving IGF1R is associated with clinical

features of macrocephaly, over growth and mental

retardation. Indeed high resolution array-CGH can

be successfully used to detect cryptic imbalances at

the chromosomal breakpoints97

.

• To rule out genomic alterations in clinically suspected

cases having normal chromosomal constitution25,97-106

Since several years various international centres are

actively involved for diagnosis in constitutional

genetics using array-CGH and came to a conclusion

that in cases of psychomotor delay/congenital

malformation, when the results of CC are normal, the

pick-up rate of interstitial micro-deletion/duplication

after proper clinical history is around 2-3% using

high-resolution karyotype and additional 2-5% cases

are diagnosed using targeted telomeric region studies

(FISH or MLPA).

Fig. 4–(a): metaphase showing additional genetic material on #8p:46,XX,add(8) † (8;?)(p23;?) (b): Schematic representation shows

8p23.3p23.1 deletion of 8.3 Mb (c): Schematic representation shows 15q23q26.3 duplication of 42.2 Mb


785

Nonetheless, around 6-30% abnormities were

detected using array- CGH after selecting various

criteria such as cytogenetic interpretation, molecular

analysis along with clinical sign and symptoms107-113

.

Array- CGH distinguishes on average 10-20% of

anomaly in patients having psychomotor delay along

with more or less congenital malformations. Deletion

is observed in two third and duplication in one third

of the cases114

.

The published results point out the potential of this

technology and its power concerning the detection of

cryptic chromosomal alterations in cases having

mental retardation (Fig. 6)112,113,115,116

.

CGH-array can replace high resolution karyotyping

in confirming clinical diagnosis in the medium term

and the standard cytogenetics will always remain the

gold standard at the time of reference and the

anomalies detected by array-CGH will be further

validated using FISH analysis for deletions and

quantitative-PCR for duplications smaller than 2 Mb.

Limitations

• Although array-CGH has proved to be an efficient

and reproducible technique, there are some

limitations. Array-CGH could not easily

characterize the structural configuration of

balanced chromosomal anomalies. Particularly the

order and orientation of the rearranged segments

cannot be determined. Also, low-level mosaicism

(i.e. < 30%) may be difficult to detect.

• Structural alteration involving heterochromatic

region cannot be detected. [unpublished data]

• DNA of same sex is used as control in array-CGH,

however in cases where the case subject is female

having two X chromosomes and marker is of

Y origin, then this Y chromosome cannot be

identified117

.

• The choice between the uses of BAC/PAC or

oligonucleotide array solely depends on the quality

of manufacture’s slides and designing of the

probes, reproducibility of the technology,

robustness of the developed statistical tool, analysis

of the results and level of resolution. The choice of

Fig. 5 – (a): Metaphase showing presence of marker chromosome

[47,XX,+mar] (b): Schematic representation shows

18p11.332p11.31 duplication of 14.9 Mb

Fig. 6–Potential of array-CGH in mental retardation


786

technology is the result of comparison between

cost and resolution we expect.

• Most of the false results (negative / positive) are

consequential from poor hybridization, linked to

bad quality DNA or it is above recognizable

threshold.

• Last but not the least is the differentiation between

real polymorphism and potentially pathogenic

polymorphism as it is also present in a normal

parent. Therefore, before applying array-CGH as a

routine diagnostic tool, a better knowledge of these

polymorphisms is obligatory.

Conclusion Array-CGH allow testing a huge number of loci in

one experiment and it is likely that it will replace

FISH approach to characterize deletion/duplication

breakpoints or to screen for known micro-deletion

syndromes and sub-telomeric imbalances. Array-CGH

is faster, has a better resolution, is a wonderful tool to

screen pangenomic and constitutes the “Connecting

Link” between CC and molecular biology for the

detection of cryptic quantitative genomic alterations.

Array-CGH is still at a high cost and requires

expensive apparatus for analysis and an expensive

technical environment, as well as a good level of

expertise. This can be partly supplemented by the

choice of the appropriate array and its resolution in

the quantification (losses or gains) of the genomic

modifications.

Acknowledgement This work was supported by UICC (International

Union against Cancer), Geneva, Switzerland and

Department of Biotechnology, India (BT/PR/9111

/MED/12/337/2007). Thanks are also due to Dr.

Jayesh Sheth for comments.

References 1 Lejeune J, Gautier M & Turpin R, Etude des chromosomes

somatiques de neuf enfants Mongolians, C R Acad Sci Paris,

248 (1959) 1721

2 Pardue ML & Gall JG, Molecular hybridization of

radioactive DNA to the DNA of cytological preparations,

Proc Natl Acad Sci USA, 64 (1969) 600

3 Yunis J, High resolution of Human chromosome, Science,

191 (1976) 1268.

4 Harper ME & Saunders GF, Localization of single copy

DNA sequences on G banded human chromosomes by in situ

hybridization, Chromosoma, 83 (1981) 431.

5 Langent JE, Jansen in de Wal N &Baan R, 2-

acetylaminofluorene modifide probes for the indirect

hybridocytochemical detection of specific nucleic acid

sequences, Exp Cell Res, 153 (1984) 61.

6 Cremer T, Landegent J, Bruckner A, Scholl H, Schardin M,

Hager H, Devilee P, Pearson P & Ploeg van der M, Detection

of chromosome aberrations in the human interphase nucleus

by visualization of specific target DNAs with radioactive and

non-radioactive in situ hydridization techniques: Diagnosis

of trisomy 18 with probe L1.84, Hum Genet, 74 (1986) 346.

7 Pinkel D, Straume T & Gray J, Cytogenetic analysis using

quantitative, high-sensitivity, fluorescence hybridization,

Proc Natl Acad Sci U S A, 83 (1986) 2934.

8 Nederlof P, Robinson D, Abuknesha R, Wiegant J, Hopman

A, Tanke H & Raap A, Three-color fluorescence in situ

hybridization for the simultaneous detection of multiple

nucleic acid sequences, Cytometry, 10 (1989) 20.

9 Koch JE, Kølvraa S, Petersen KB, Gregersen N & Bolund L,

Oligonucleotide-priming methods for the chromosome-

specific labelling of alpha satellite DNA in situ,

Chromosoma, 98 (1989) 259.

10 Tkachuk DC, Westbrook CA, Andreeff M, Donlon TA,

Cleary ML, Suryanarayan K, Homge M, Redner A, Gray J &

Pinkel D, Detection of bcr-abl fusion in chronic myelo-

geneous leukemia by in situ hybridization, Science, 250

(1990) 559.

11 Nederlof PM, van der Flier S, Wiegant J, Raap AK, Tanke

HJ, Ploem JS & van der Ploeg M, Multiple fluorescence in

situ hybridization, Cytometry, 11 (1990) 126.

12 Kallioniemi A, Kallioniemi O, Sudar D, Rutovitz D, Gray J,

Waldman F & Pinkel D, Comparative genomic hybridization

for molecular cytogenetic analysis of solid tumors, Science,

258 (1992) 818.

13 Parra I & Windle B, High resolution visual mapping of

stretched DNA by fluorescent hybridization, Nat Genet, 5

(1993) 4.

14 Speicher M, Gwyn Ballard S & Ward D, Karyotyping human

chromosomes by combinatorial multi-fluor FISH, Nat Genet,

12 (1996) 368.

15 Schröck E, du Manoir S, Veldman T, Schoell B, Wienberg J,

Ferguson-Smith M, Ning Y, Ledbetter D, Bar-Am I,

Soenksen D, Garini Y & Ried T, Multicolor spectral

karyotyping of human chromosomes, Science, 273 (1996)

494.

16 Müller S, Rocchi M, Ferguson-Smith M & Wienberg J,

Toward a multicolor chromosome bar code for the entire

human karyotype by fluorescence in situ hybridization, Hum

Genet, 100 (1997) 271.

17 Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J,

Benner A, Dohner H, Cremer T & Lichter P, Matrix-based

comparative genomic hybridization: biochips to screen

for genomic imbalances, Genes Chromosome Cancer, 20

(1997) 399.

18 Nilsson M, Krejci K, Koch J, Kwiatkowski M, Gustavsson P

& Landegren U, Padlock probes reveal single-nucleotide

differences, parent of origin and in situ distribution of

centromeric sequences in human chromosomes 13 and 21,

Nat Genet, 16 (1997) 252.

19 Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D,

Collins C, Kuo W L, Chen C, Zhai Y, Dairkee S H, Ljung B

M, Gray J W & Albertson D G, High resolution analysis of

DNA copy number variation using comparative genomic

hybridization to micro-arrays, Nat Genet, 20 (1998) 207.


787

20 Albertson D G, Ylstra B, Segraves R, Collins C, Dairkee S

H, Kowbel D, Kuo W L, Gray J W & Pinkel D, Quantitative

mapping of amplicon structure by array CGH identifies

CYP24 as a candidate oncogene, Nat Genet, 25(2)

(2000) 144.

21 Maas N M, Van Buggenhout G, Hannes F, Thienpont B,

Sanlaville D, Kok K, Midro A, Andrieux J, Anderlid B M,

Schoumans J, Hordijk R, Devriendt K, Fryns J P &

Vermeesch J R, Genotype-phenotype correlation in 21

patients with Wolf-Hirschhorn syndrome using high

resolution array comparative genome hybridization (CGH),

J Med Genet, 45(2) (2008) 71.

22 Veltman J A, Schoenmakers E F, Eussen B H, Janssen I,

Merkx G, van Cleef B, van Ravenswaaij C M, Brunner H G,

Smeets D & Van Kessel A G, High-throughput analysis of

subtelomeric chromosome rearrangements by use of array-

based comparative genomic hybridization, Am J Hum Genet,

70 (2002) 1269.

23 Vermeesch J R, Melotte C, Froyen G, Van Vooren S, Dutta

B, Maas N, Vermeulen S, Menten B, Speleman F, De Moor

B, Van Hummelen P, Marynen P, Fryns J P & Devriendt K,

Molecular karyotyping: array CGH quality criteria for

constitutional genetic diagnosis, J Histochem Cytochem, 53

(2005)13.

24 Sanlaville D, Lapierre J M, Turleau C, Coquin A, Borck G,

Colleaux L, Vekemans M & Romana S P, Molecular

karyotyping in human constitutional cytogenetics, Eur J Med

Genet, 48 (2005) 214.

25 Andrieux J, Array-CGH for routine diagnosis of cryptic

chromosomal imbalances, Pathol Biol 56 (2008) 368-74.

26 Ishkanian A S, Malloff C A, Watson S K, DeLeeuw R J,

Chi B, Coe B P, Snijders A, Albertson D G, Pinkel D, Marra

M A, Ling V, MacAulay C & Lam W L, A tiling resolution

DNA microarray with complete coverage of the human

genome, Nat Genet, 36(3) (2004) 299.

27 Barrett M T, Scheffer A, Ben-Dor A, Sampas N, Lipson D,

Kincaid R, Tsang P, Curry B, Baird K, Meltzer P S,

Yakhini Z, Bruhn L & Laderman S, Comparative genomic

hybridization using oligonucleotide microarrays and total

genomic DNA, Proc Natl Acad Sci, 101 (2004)11765.

28 Komura D, Shen F, Ishikawa S, Fitch K R, Chen W, Zhang J,

Liu G, Ihara S, Nakamura H, Hurles M E, Lee C, Scherer S

W, Jones K W, Shapero M H, Huang J & Aburatani H,

Genome-wide detection of human copy number variations

using highdensity DNA oligonucleotide arrays, Genome Res,

16 (2006)1575.

29 Suela J, Alvarez S & Cigudosa JC, DNA profiling by

arrayCGH in acute myeloid leukemia and myelodysplastic

syndromes, Cytogenet Genome Res, 118 (2007) 304.

30 Tyybäkinoja A, Elonen E, Piippo K, Porkka K & Knuutila S,

Oligonucleotide array-CGH reveals cryptic gene copy

number alterations in karyotypically normal acute myeloid

leukemia. Leukemia, 21 (2007) 571,

31 Rücker FG, Bullinger L, Schwaenen C, Lipka DB,

Wessendorf S, Fröhling S, Bentz M, Miller S, Scholl C,

Schlenk RF, Radlwimmer B, Kestler HA, Pollack JR, Lichter

P, Döhner K & Döhner H, Disclosure of candidate genes in

acute myeloid leukemia with complex karyotypes using

microarray-based molecular characterization, J Clin Oncol,

24 (2006) 3887.

32 Paulsson K, Heidenblad M, Strömbeck B, Staaf J, Jönsson G,

Borg A, Fioretos T & Johansson B, High-resolution genome-

wide array-based comparative genome hybridization reveals

cryptic chromosome changes in AML and MDS cases with

trisomy 8 as the sole cytogenetic aberration, Leukemia, 20

(2006) 840.

33 Tyybäkinoja A, Saarinen-Pihkala U, Elonen E & Knuutila S,

Amplified, lost and fused genes in 11q23-25 amplicon in

acute myeloid leukemia, an array-CGH study, Genes

Chromosomes Cancer 45 (2006) 257.

34 Martínez-Ramírez A, Urioste M, Melchor L, Blesa D, Valle

L, de Andrés SA, Kok K, Calasanz MJ, Cigudosa JC &

Benítez J, Analysis of myelodysplastic syndromes with

complex karyotypes by high-resolution comparative genomic

hybridization and subtelomeric CGH array, Genes

Chromosomes Cancer 42 (2005) 287.

35 Davidsson J, Andersson A, Paulsson K, Heidenblad M,

Isaksson M, Borg A, Heldrup J, Behrendtz M, Panagopoulos

I, Fioretos T & Johansson B, Tiling resolution array

comparative genomic hybridization, expression and

methylation analyses of dup(1q) in Burkitt lymphomas and

pediatric high hyperdiploid acute lymphoblastic leukemias

reveal clustered near-centromeric breakpoints and

overexpression of genes in 1q22-32.3, Hum Mol Genet 16

(2007) 2215.

36 Clappier E, Cuccuini W, Kalota A, Crinquette A, Cayuela

JM, Dik WA, Langerak AW, Montpellier B, Nadel B,

Walrafen P, Delattre O, Aurias A, Leblanc T, Dombret H,

Gewirtz AM, Baruchel A, Sigaux F & Soulier J, The C-MYB

locus is involved in chromosomal translocation and genomic

duplications in human T-cell acute leukemia (T-ALL), the

translocation defining a new T-ALL subtype in very young

children, Blood 110 (2007) 1251.

37 Kuchinskaya E, Nordgren A, Heyman M, Schoumans J,

Corcoran M, Staaf J, Borg A, Söderhäll S, Grandér D,

Nordenskjöld M & Blennow E, Tiling-resolution array-CGH

reveals the pattern of DNA copy number alterations in acute

lymphoblastic leukemia with 21q amplification: the result of

telomere dysfunction and breakage/fusion/breakage cycles,

Leukemia, 21 (2007) 1327.

38 Schoumans J, Johansson B, Corcoran M, Kuchinskaya E,

Golovleva I, Grandér D, Forestier E, Staaf J, Borg A,

Gustafsson B, Blennow E & Nordgren A, Characterisation of

dic(9;20)(p11-13;q11) in childhood B-cell precursor acute

lymphoblastic leukaemia by tiling resolution array-based

comparative genomic hybridisation reveals clustered

breakpoints at 9p13.2 and 20q11.2, Br J Haematol, 135

(2006) 492.

39 Paulsson K, Heidenblad M, Mörse H, Borg A, Fioretos T &

Johansson B, Identification of cryptic aberrations and

characterization of translocation breakpoints using array

CGH in high hyperdiploid childhood acute lymphoblastic

leukemia, Leukemia 20 (2006) 2002.

40 van Vlierberghe P, Meijerink JP, Lee C, Ferrando AA, Look

AT, van Wering ER, Beverloo HB, Aster JC & Pieters R, A

new recurrent 9q34 duplication in pediatric T-cell acute

lymphoblastic leukemia, Leukemia, 20 (2006) 1245.

41 Lilljebjörn H, Heidenblad M, Nilsson B, Lassen C, Horvat A,

Heldrup J, Behrendtz M, Johansson B, Andersson A

& Fioretos T, Combined high-resolution array-based


788

comparative genomic hybridization and expression profiling

of ETV6/RUNX1-positive acute lymphoblastic leukemias

reveal a high incidence of cryptic Xq duplications and

identify several putative target genes within the commonly

gained region, Leukemia, 21 (2007) 2137.

42 Hosoya N, Sanada M, Nannya Y, Nakazaki K, Wang L,

Hangaishi A, Kurokawa M, Chiba S & Ogawa S,

Genomewide screening of DNA copy number changes in

chronic myelogenous leukemia with the use of high-

resolution array-based comparative genomic hybridization,

Genes Chromosomes Cancer, 45 (2006) 82.

43 Patel A, Kang SH, Lennon PA, Li YF, Rao PN, Abruzzo L,

Shaw C, Chinault AC & Cheung SW, Validation of a

targeted DNA microarray for clinical evaluation of recurrent

abnormalities in chronic lymphocytic leukemia, Am J

Hematol 83 (2008) 540.

44 Tyybakinoja A, Vilpo J & Knuutila S, High-resolution

oligonucleotide array-CGH pinpoints genes involved in

cryptic losses in chronic lymphocytic leukemia, Cytogenet

Genome Res 118 (2007) 8.

45 Rubio-Moscardo F, Climent J, Siebert R, Piris MA, Martín-

Subero JI, Nieländer I, Garcia-Conde J, Dyer MJ, Terol MJ,

Pinkel D & Martinez-Climent JA, Mantle-cell lymphoma

genotypes identified with CGH to BAC microarrays define a

leukemic subgroup of disease and predict patient outcome,

Blood, 105 (2005) 4445.

46 Wessendorf S, Barth TF, Viardot A, Mueller A, Kestler HA,

Kohlhammer H, Lichter P, Bentz M, Döhner H, Möller P &

Schwaenen C, Further delineation of chromosomal

consensus regions in primary mediastinal B-cell lymphomas:

an analysis of 37 tumor samples using high-resolution

genomic profiling (array-CGH), Leukemia, 21 (2007) 2463.

47 Kim WS, Honma K, Karnan S, Tagawa H, Kim YD, Oh YL,

Seto M & Ko YH, Genome-wide array-based comparative

genomic hybridization of ocular marginal zone B cell

lymphoma: comparison with pulmonary and nodal marginal

zone B cell lymphoma, Genes Chromosomes Cancer 46

(2007) 776.

48 Mestre-Escorihuela C, Rubio-Moscardo F, Richter JA,

Siebert R, Climent J, Fresquet V, Beltran E, Agirre X,

Marugan I, Marín M, Rosenwald A, Sugimoto KJ, Wheat

LM, Karran EL, García JF, Sanchez L, Prosper F, Staudt

LM, Pinkel D, Dyer MJ & Martinez-Climent JA,

Homozygous deletions localize novel tumor suppressor

genes in B-cell lymphomas, Blood, 109 (2007) 271.

49 Fukuhara N, Tagawa H, Kameoka Y, Kasugai Y, Karnan S,

Kameoka J, Sasaki T, Morishima Y, Nakamura S & Seto M,

Characterization of target genes at the 2p15-16 amplicon in

diffuse large B-cell lymphoma, Cancer Sci, 97 ( 2006) 499.

50 Chen W, Houldsworth J, Olshen AB, Nanjangud G, Chaganti

S, Venkatraman ES, Halaas J, Teruya-Feldstein J, Zelenetz

AD & Chaganti RS, Array comparative genomic

hybridization reveals genomic copy number changes

associated with outcome in diffuse large B-cell lymphomas,

Blood, 107 (2006) 2477.

51 Largo C, Alvarez S, Saez B, Blesa D, Martin-Subero JI,

González-García I, Brieva JA, Dopazo J, Siebert R, Calasanz

MJ & Cigudosa JC, Identification of overexpressed genes in

frequently gained/amplified chromosome regions in multiple

myeloma, Haematologica, 91 (2006) 184.

52 Largo C, Saéz B, Alvarez S, Suela J, Ferreira B, Blesa D,

Prosper F, Calasanz MJ & Cigudosa JC, Multiple myeloma

primary cells show a highly rearranged unbalanced genome

with amplifications and homozygous deletions irrespective of

the presence of immunoglobulin-related chromosome

translocations, Haematologica, 92 (2007) 795.

53 Lindholm PM, Salmenkivi K, Vauhkonen H, Nicholson AG,

Anttila S, Kinnula VL & Knuutila S, Gene copy number

analysis in malignant pleural mesothelioma using

oligonucleotide array CGH, Cytogenet Genome Res, 119

(2007) 119 46.

54 Zanazzi C, Hersmus R, Veltman IM, Gillis AJ, van Drunen

E, Beverloo HB, Hegmans JP, Verweij M, Lambrecht BN,

Oosterhuis JW & Looijenga LH, Gene expression profiling

and gene copy-number changes in malignant mesothelioma

cell lines, Genes Chromosomes Cancer, 46 (2007) 895.

55 Schulten HJ, Perske C, Thelen P, Polten A, Borst C,

Gunawan B & Nagel H, Establishment and characterization

of two distinct malignant mesothelioma cell lines with

common clonal origin, Cancer Genet Cytogenet, 176

(2007) 35.

56 Rouleau E, Lefol C, Tozlu S, Andrieu C, Guy C, Copigny F,

Nogues C, Bieche I & Lidereau R, High-resolution

oligonucleotide array-CGH applied to the detection and

characterization of large rearrangements in the hereditary

breast cancer gene BRCA1, Clin Genet, 72 (2007) 199.

57 Melchor L, Honrado E, García MJ, Alvarez S, Palacios J,

Osorio A, Nathanson KL & Benítez J, Distinct genomic

aberration patterns are found in familial breast cancer

associated with different immunohistochemical subtypes,

Oncogene 27 (2008) 3165.

58 Johnson N, Speirs V, Curtin NJ & Hall AG, A comparative

study of genome-wide SNP, CGH microarray and protein

expression analysis to explore genotypic and phenotypic

mechanisms of acquired antiestrogen resistance in breast

cancer, Breast Cancer Res Treat 111 (2008) 55

59 Climent J, Garcia JL, Mao JH, Arsuaga J & Perez-Losada J,

Characterization of breast cancer by array comparative

genomic hybridization, Biochem Cell Biol 85 (2007) 497.

60 Vincent-Salomon A, Gruel N, Lucchesi C, MacGrogan G,

Dendale R, Sigal-Zafrani B, Longy M, Raynal V, Pierron G,

de Mascarel I, Taris C, Stoppa-Lyonnet D, Pierga JY,

Salmon R, Sastre-Garau X, Fourquet A, Delattre O, de

Cremoux P & Aurias A, Identification of typical medullary

breast carcinoma as a genomic sub-group of basal-like

carcinomas, a heterogeneous new molecular entity, Breast

Cancer Res, 9 (2007) R24.

61 Orsetti B, Nugoli M, Cervera N, Lasorsa L, Chuchana P,

Rougé C, Ursule L, Nguyen C, Bibeau F, Rodriguez C &

Theillet C, Genetic profiling of chromosome 1 in breast

cancer: mapping of regions of gains and losses and

identification of candidate genes on 1q, Br J Cancer, 95

(2006) 1439.

62 Bergamaschi A, Kim YH, Wang P, Sørlie T, Hernandez-

Boussard T, Lonning PE, Tibshirani R, Børresen-Dale AL &

Pollack JR, Distinct patterns of DNA copy number alteration

are associated with different clinicopathological features

and gene-expression subtypes of breast cancer, Genes

Chromosomes Cancer, 45 (2006) 1033.

63 van Beers EH & Nederlof PM, Array-CGH and breast

cancer, Breast Cancer Res, 8 (2006) 210.


789

64 Nowee ME, Snijders AM, Rockx DA, de Wit RM, Kosma

VM, Hämäläinen K, Schouten JP, Verheijen RH, van Diest

PJ, Albertson DG & Dorsman JC, DNA profiling of primary

serous ovarian and fallopian tube carcinomas with array

comparative genomic hybridization and multiplex ligation-

dependent probe amplification, J Pathol, 213 (2007) 46.

65 Mayr D, Kanitz V, Anderegg B, Luthardt B, Engel J, Löhrs

U, Amann G & Diebold J, Analysis of gene amplification

and prognostic markers in ovarian cancer using comparative

genomic hybridization for microarrays and immunohisto-

chemical analysis for tissue microarrays, Am J Clin Pathol,

126 (2006) 101.

66 Fijneman RJ, Carvalho B, Postma C, Mongera S, van

Hinsbergh VW & Meijer GA, Loss of 1p36, gain of 8q24,

and loss of 9q34 are associated with stroma percentage of

colorectal cancer, Cancer Lett, 258 (2007) 223.

67 Fensterer H, Radlwimmer B, Sträter J, Buchholz M, Aust

DE, Julié C, Radvanyi F, Nordlinger B, Belluco C, Van

Cutsem E, Köhne CH, Kestler HA, Schwaenen C, Nessling

M, Lutz MP, Lichter P, Gress TM & EORTC

Gastrointestinal (GI) Group, Matrix-comparative genomic

hybridization from multicenter formalin-fixed paraffin-

embedded colorectal cancer tissue blocks, BMC Cancer, 7

(2007) 58.

68 Lassmann S, Weis R, Makowiec F, Roth J, Danciu M, Hopt

U & Werner M, Array CGH identifies distinct DNA copy

number profiles of oncogenes and tumor suppressor genes in

chromosomal- and microsatellite-unstable sporadic colorectal

carcinomas, J Mol Med, 85 (2007) 293.

69 Sun B, Wu J, Zhang T & Wang C, High-resolution analysis

of genomic profiles of hepatocellular carcinoma cells with

differential osteopontin expression, Cancer Biol Ther

7 (2008) 387

70 Steinemann D, Skawran B, Becker T, Tauscher M,

Weigmann A, Wingen L, Tauscher S, Hinrichsen T, Hertz S,

Flemming P, Flik J, Wiese B, Kreipe H, Lichter P,

Schlegelberger B & Wilkens L, Assessment of differentiation

and progression of hepatic tumors using array-based

comparative genomic hybridization, Clin Gastroenterol

Hepatol, 4 (2006) 1283.

71 Park SJ, Jeong SY & Kim HJ, Y chromosome loss and other

genomic alterations in hepatocellular carcinoma cell lines

analyzed by CGH and CGH array, Cancer Genet Cytogenet,

166 (2006) 56.

72 Harada T, Chelala C, Bhakta V, Chaplin T, Caulee K, Baril

P, Young BD & Lemoine NR, Genome-wide DNA copy

number analysis in pancreatic cancer using high-density

single nucleotide polymorphism arrays, Oncogene 27

(2008) 1951

73 Harada T, Baril P, Gangeswaran R, Kelly G, Chelala C,

Bhakta V, Caulee K, Mahon PC & Lemoine NR,

Identification of genetic alterations in pancreatic cancer by

the combined use of tissue microdissection and array-based

comparative genomic hybridisation, Br J Cancer, 96

(2007) 373.

74 Yamamoto Y, Chochi Y, Matsuyama H, Eguchi S, Kawauchi

S, Furuya T, Oga A, Kang JJ, Naito K & Sasaki K, Gain of

5p15.33 is associated with progression of bladder cancer,

Oncology, 72 (2007) 132.

75 Vauhkonen H, Böhling T, Eissa S, Shoman S & Knuutila S,

Can bladder adenocarcinomas be distinguished from

schistosomiasis-associated bladder cancers by using array

comparative genomic hybridization analysis? Cancer Genet

Cytogenet, 177 (2007) 153.

76 Blaveri E, Brewer JL, Roydasgupta R, Fridlyand J, DeVries

S, Koppie T, Pejavar S, Mehta K, Carroll P, Simko JP &

Waldman FM, Bladder cancer stage and outcome by array-

based comparative genomic hybridization, Clin Cancer Res,

11 (2005) 7012.

77 Lapointe J, Li C, Giacomini CP, Salari K, Huang S, Wang P,

Ferrari M, Hernandez-Boussard T, Brooks JD & Pollack JR,

Genomic profiling reveals alternative genetic pathways of

prostate tumorigenesis, Cancer Res, 67 (2007) 8504.

78 Paris PL, Sridharan S, Scheffer A, Tsalenko A, Bruhn L &

Collins C, High resolution oligonucleotide CGH using DNA

from archived prostate tissue, Prostate, 67 (2007) 1447.

79 Sun J, Liu W, Adams TS, Sun J, Li X, Turner AR, Chang B,

Kim JW, Zheng SL, Isaacs WB & Xu J, DNA copy number

alterations in prostate cancers: a combined analysis of

published CGH studies, Prostate, 67 (2007) 692.

80 Stallings RL, Origin and functional significance of large-

scale chromosomal imbalances in neuroblastoma, Cytogenet

Genome Res, 118 (2007) 110.

81 Do JH, Kim IS, Park TK & Choi DK, Genome-wide

examination of chromosomal aberrations in neuroblastoma

SH-SY5Y cells by array-based comparative genomic

hybridization, Mol Cells, 24 (2007) 105.

82 Scaruffi P, Coco S, Cifuentes F, Albino D, Nair M,

Defferrari R, Mazzocco K & Tonini GP, Identification and

characterization of DNA imbalances in neuroblastoma by

high-resolution oligonucleotide array comparative genomic

hybridization, Cancer Genet Cytogenet, 177 (2007) 20.

83 Mosse YP, Diskin SJ, Wasserman N, Rinaldi K, Attiyeh EF,

Cole K, Jagannathan J, Bhambhani K, Winter C & Maris JM,

Neuroblastomas have distinct genomic DNA profiles that

predict clinical phenotype and regional gene expression,


84 Korshunov A, Sycheva R & Golanov A, Genetically distinct

and clinically relevant subtypes of glioblastoma defined by

array-based comparative genomic hybridization (array-

CGH), Acta Neuropathol, 111 (2006) 465.

85 Korshunov A, Sycheva R, Golanov A & Pronin I, Gains at

the 1p36 chromosomal region are associated with

symptomatic leptomeningeal dissemination of supratentorial

glioblastomas, Am J Clin Pathol, 127 (2007) 585.

86 Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI,

Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P &

Meléndez B, Identification of novel candidate target genes in

amplicons of Glioblastoma multiforme tumors detected by

expression and CGH microarray profiling, Mol Cancer, 5

(2006) 39.

87 Rossi MR, Conroy J, McQuaid D, Nowak NJ, Rutka JT &

Cowell JK, Array CGH analysis of pediatric medulloblastomas,


88 Pfister S, Remke M, Toedt G, Werft W, Benner A,

Mendrzyk F, Wittmann A, Devens F, von Hoff K, Rutkowski

S, Kulozik A, Radlwimmer B, Scheurlen W, Lichter P &

Korshunov A, Supratentorial primitive neuroectodermal

tumors of the central nervous system frequently harbor

deletions of the CDKN2A locus and other genomic

aberrations distinct from medulloblastomas, Genes

Chromosomes Cancer, 46 (2007) 839.


790

89 Rodrigues R, Roque L, Espadinha C, Pinto A, Domingues R,

Dinis J, Catarino A, Pereira T & Leite V, Comparative

genomic hybridization, BRAF, RAS, RET, and oligo-array

analysis in aneuploid papillary thyroid carcinomas, Oncol

Rep, 18 (2007) 917.

90 Finn S, Smyth P, O'Regan E, Cahill S, Toner M, Timon C,

Flavin R, O'Leary J & Sheils O, Low-level genomic

instability is a feature of papillary thyroid carcinoma: an

array comparative genomic hybridization study of laser

capture microdissected papillary thyroid carcinoma tumors

and clonal cell lines, Arch Pathol Lab Med, 131 (2007) 65.

91 Lee GY, Yang WI, Jeung HC, Kim SC, Seo MY, Park CH,

Chung HC & Rha SY, Genome-wide genetic aberrations of

thymoma using cDNA microarray based comparative

genomic hybridization, BMC Genomics, 8 (2007) 305.

92 Kallioniemi A, CGH micro-arrays and cancer, Curr Opin

Biotechnol, 19 (2008) 6.

93 Sheth FJ, Andrieux J & Sheth JJ, Marker chromosome in a

child with microcephaly and mental retardation characterize

by array-CGH as trisomy 18p. Ind Pediatr (2009) [In Press]

94 Andrieux J, Richebourg S, Duban-Bedu B, Petit F, Leprêtre

F, Sukno S, Dehouck MB & Delobel B, Characterization by

array-CGH of an interstitial de novo tandem 6p21.2p22.1

duplication in a boy with epilepsy and developmental delay,

Eur J Med Genet, 51 (2008) 373.

95 Doco-Fenzy M, Holder-Espinasse M, Bieth E, Magdelaine

C, Vincent MC, Khoury M, Andrieux J, Zhang F, Lupski JR,

Klink R, Schneider A, Goze-Martineau O, Cuisset JM,

Vallee L, Manouvrier-Hanu S, Gaillard D & de Martinville

B, The clinical spectrum associated with a chromosome 17

short arm proximal duplication (dup 17p11.2) in three

patients, Am J Med Genet, 146 (2008) 917.

96 Maas NM, Van Buggenhout G, Hannes F, Thienpont B,

Sanlaville D, Kok K, Midro A, Andrieux J, Anderlid BM,

Schoumans J, Hordijk R, Devriendt K, Fryns JP &

Vermeesch JR, Genotype-phenotype correlation in 21

patients with Wolf-Hirschhorn syndrome using high

resolution array comparative genome hybridisation (CGH), J

Med Genet, 45 (2008) 71.

97 Leal T, Andrieux J, Duban-Bedu B, Bouquillon S, Brevière

GM & Delobel B, Array-CGH detection of a de novo 0.8Mb

deletion in 19q13.32 associated with mental retardation,

cardiac malformation, cleft lip and palate, hearing loss and

multiple dysmorphic features, Eur J Med Genet, 52 (2009) 62

98 Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L,

Fiegler H, Firth H, Sanlaville D, Winter R, Colleaux L,

Bobrow M & Carter N P, Micro-array based comparative

genomic hybridization (array-CGH) detects submicroscopic

chromosomal deletions and duplications in patients with

learning disability/mental retardation and dysmorphic

features, J Med Genet, 41 (2004) 241.

99 Lockwood W W, Chari R, Chi B & Lam W L, Recent

advances in array comparative genomic hybridization

technologies and their applications in human genetics, Eur J

Hum Genet, 14 (2006)139.

100 de Vries B B, Pfundt R, Leisink M, Koolen D A, Vissers L

E, Janssen I M, Reijmersdal S, Nillesen W M, Huys E H,

Leeuw N, Smeets D, Sistermans E A, Feuth T, van

Ravenswaaij-Arts C M, van Kessel A G, Schoenmakers E F,

Brunner H G & Veltman J A, Diagnostic genome profiling in

mental retardation, Am J Hum Genet, 77 (2005) 606.

101 Shaffer LG & Bejjani BA, Medical applications of array

CGH and the transformation of clinical cytogenetics,

Cytogenet Genome Res, 115 (2006) 303.

102 Veltman JA, Genomic microarrays in clinical diagnosis,

Curr Opin Pediatr, 18 (2006) 598.

103 Shaffer LG, Bejjani BA, Torchia B, Kirkpatrick S,

Coppinger J & Ballif BC, The identification of micro-

deletion syndromes and other chromosome abnormalities:

cytogenetic methods of the past, new technologies for the

future, Am J Med Genet C Semin Med Genet, 145C(4)

(2007) 335.

104 Doco-Fenzy M, Landais E, Andrieux J, Schneider A,

Delemer B, Sulmont V, Melin JP, Ploton D, Thevenard J,

Monboisse JC, Belouadah M, Lefebvre F, Durlach A,

Goossens M, Albuisson J, Motte J & Gaillard D, Deletion

2q36.2q36.3 with multiple renal cysts and severe mental

retardation, Eur J Med Genet, 51 (2008) 598.

105 Andrieux J, Lepretre F, Cuisset JM, Goldenberg A, Delobel

B, Manouvrier-Hanu S & Holder-Espinasse M, Deletion

18q21.2q21.32 involving TCF4 in a boy diagnosed by CGH-

array, Eur J Med Genet, 51 (2008) 172-7.

106 Andrieux J, Cuvellier JC, Duban-Bedu B, Joriot-Chekaf S,

Dieux-Coeslier A, Manouvrier-Hanu S, Delobel B & Vallee

L, A 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication in a

boy with extreme microcephaly with simplified gyral pattern,

vermis hypoplasia and corpus callosum agenesis, Eur J Med

Genet, 51 (2008) 87-91

107 Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L,

Fiegler H, Firth H, Sanlaville D, Winter R, Colleaux L,

Bobrow M & Carter N P, Micro-array based comparative

genomic hybridization (array-CGH) detects submicroscopic

chromosomal deletions and duplications in patients with

learning disability/mental retardation and dysmorphic

features, J Med Genet, 41 (2004) 241.

108 Shaffer LG & Bejjani BA, Medical applications of array

CGH and the transformation of clinical cytogenetics,

Cytogenet Genome Res, 115 (2006) 303.

109 Shaffer LG, Bejjani BA, Torchia B, Kirkpatrick S,

Coppinger J & Ballif BC, The identification of microdeletion

syndromes and other chromosome abnormalities: cytogenetic

methods of the past, new technologies for the future, Am J

Med Genet C Semin Med Genet, 145 ( 2007) 335.

110 Béri-Dexheimer M, Bonnet C, Chambon P, Brochet K,

Grégoire MJ & Jonveaux P, Microarray-based comparative

genomic hybridization in the study of constitutional

chromosomal abnormalities, Pathol Biol, 55(1) (2007)13.

111 Vissers LE, de Vries BB, Osoegawa K, Janssen IM, Feuth T,

Choy CO, Straatman H, van der Vliet W, Huys EH, van Rijk

A, Smeets D, van Ravenswaaij-Arts CM, Knoers N , van der

Burgt I, de Jong PJ, Brunner HG, van Kessel AG,

Schoenmakers EF & Veltman JA, Array-based comparative

genomic hybridization for the genomewide detection of

submicroscopic chromosomal abnormalities, Am J Hum

Genet, 73 (2003) 1261.

112 Krepischi-Santos AC, Vianna-Morgante AM, Jehee FS,

Passos-Bueno MR, Knijnenburg J, Szuhai K, Sloos W,

Mazzeu JF, Kok F, Cheroki C, Otto PA, Mingroni-Netto RC,

Varela M, Koiffmann C, Kim CA, Bertola DR, Pearson PL

& Rosenberg C, Whole-genome array-CGH screening in

undiagnosed syndromic patients: old syndromes revisited and

new alterations, Cytogenet Genome Res, 115 (2006) 254.


791

113 Rosenberg C, Knijnenburg J, Bakker E, Vianna-Morgante

AM, Sloos W, Otto PA, Kriek M, Hansson K, Krepischi-

Santos AC, Fiegler H, Carter NP, Bijlsma EK, van

Haeringen A, Szuhai K & Tanke HJ, Array-CGH

detection of micro rearrangements in mentally retarded

individuals: clinical significance of imbalances present

both in affected children and normal parent, J Med Genet,

43 (2006) 180.

114 Menten B, Maas N, Thienpont B, Buysse K, Vandesompele

J, Melotte C, de Ravel T, Van Vooren S, Balikova I, Backx

L, Janssens S, De Paepe A, De Moor B, Moreau Y, Marynen

P, Fryns JP, Mortier G, Devriendt K, Speleman F &

Vermeesch J R, Emerging patterns of cryptic chromosomal

imbalance in patients with idiopathic mental retardation and

multiple congenital anomalies: a new series of 140 patients

and review of published reports, J Med Genet, 43 (2006)

625.

115 Stankiewicz P & Beaudet AL, Use of array CGH in the

evaluation of dysmorphology, malformations, developmental

delay and idiopathic mental retardation, Curr Opin Genet

Dev, 17 (2007) 182.

116 de Ravel TJ, Devriendt K, Fryns JP & Vermeesch JR,

What’s new in karyotyping? The move towards array

comparative genomic hybridization (CGH), Eur J Pediatr,

116 (2007) 637.

117 Sheth FJ, Ewers E, Kosyakova N, Weise A, Sheth J, Patil S,

Ziegler M, Liehr T, A neocentric isochromosome Yp present

as additional small supernumerary marker chromosome –

evidence against U-type exchange mechanism? Cytogenetic

Genome Res, 125 (2) (2009) 115

comparative genomic hybridization array study and its

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