please stand by… the webinar genetic biomarkers revealed...g-ccc. cd34-fish •circulating cd34+...
TRANSCRIPT
![Page 1: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/1.jpg)
to login to Twitter and send tweets
Facebook login
if you need help
shows speaker bios
download slides and more info
LinkedIn login
shows slide window
Change the size of any window by dragging the lower right corner. Use controls in top right corner to close or maximize each window.
What each widget does:
opens the Ask a Question box
Twitter login (#ScienceWebinar)
search Wikipedia
shows the audio media player
Genetic Biomarkers Revealed: Unraveling the Complexities of Cancer Genomes in Blood Malignancies
PLEASE STAND BY… the webinar
will begin shortly…
Webinar Series Science
![Page 2: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/2.jpg)
Sponsored by:
Participating Experts:
Detlef Haase, M.D., Ph.D. University of Göttingen Germany
Stuart Schwartz, Ph.D. Labcorp Research Triangle Park, NC
Brought to you by the Science/AAAS Custom Publishing Office
Webinar Series Science
30 January 2013
Genetic Biomarkers Revealed: Unraveling the Complexities of Cancer Genomes in Blood Malignancies
![Page 3: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/3.jpg)
G-C
CC
U
nive
rsitä
tsK
rebs
zent
rum
G
-CC
C
Göt
tinge
n
Com
preh
ensi
ve C
ance
r Cen
ter
Cytogenetic Changes in MDS: – Genetic Biomarkers for Prognosis, Genetic Evolution and Personalized
Treatment Decisions
Detlef Haase and Christina Ganster Department of Hematology and Oncology
Comprehensive Cancer Center University Medicine Göttingen, Germany
Genetic Biomarkers revealed: Unraveling the Complexities of Cancer Genomes in Blood Malignancies, January 30, 2013
![Page 4: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/4.jpg)
G-C
CC
G
-CC
C
• Heterogenous group of clonal hematopoetic stem cell diseases
• Impaired differentiation, growth and function of bone marrow progenitors and peripheral blood cells with peripheral cytopenias
• Often combined defects of two or all three cell lineages
• ~30% develop acute myeloid leukemias (AML)
• Increased risk for MDS-related death (bleeding complications, infections)
• Clonal genetic abnormalities (cytogenetic and molecular) can be found in almost every patient, however are very heterogeneous
• Genetically highly dynamic with frequent genetic evolution over time
• Genetic analyses gain increasing influence for individualized treatment decisions
Definition of Myelodysplastic Syndromes (MDS)
![Page 5: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/5.jpg)
G-C
CC
G
-CC
C
• ~ 50% of pts. display clonal chromosome abnormalities by banding analysis 1
• ~ 50% of pts. show clonal chromosome abnorm. by SNP-Analyis2,3
• 50 to 70% of pts. have point mutations 4,5
Genetic Background of MDS
1Haase et al., Blood, 2007; 2Mohamedali et al., Blood 2007; Tiu et al., Blood, 2011 3Bejar et al., New Engl J Med, 2011; 4Bejar et al., JCO, 2012
49% 25%
26%
Cytogenetics SNP point mutation?
The aim: 100% informative cases by combining the methods
![Page 6: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/6.jpg)
G-C
CC
G
-CC
C
Genetic Background of MDS Short Nucleoitide Polymorphisms: In 119 low-risk MDs pts. 46% showed UPD (A), 10% deletions (B) and 8% amplifications (C)
2Mohamedali et al., Blood 2007
![Page 7: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/7.jpg)
G-C
CC
G
-CC
C
Genetic Background of MDS
Short Nucleoitide Polymorphisms:
Mohamedali et al., Blood 2007;110:3365-3373
„ SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions“
![Page 8: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/8.jpg)
G-C
CC
G
-CC
C
• Normal/non informative MC: 54% clonal abnormalities by SNP
• MC abnormal: 62% additional SNP-changes
Genetic Background of MDS Short Nucleoitide Polymorphisms: Comparative analysis of metaphase cytogenetics (MC) and SNP-Analysis in 430 pts. (MDS=250, MDS/MPN=95, Sec. AML=85):
Tiu et al., Blood 2011;117(17):4552-60
49%
44%
7%
MC normal aberrant no information
26%
74%
MC + SNP normal aberrant
![Page 9: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/9.jpg)
G-C
CC
G
-CC
C
Combined (MC + SNP) prognostic scoring system
Tiu et al., Blood 2011;117(17):4552-60
• Cytogenetic risk groups according to old IPSS were considered
![Page 10: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/10.jpg)
G-C
CC
G
-CC
C
Genetic Evolution of MDS
AML
?
complex Trisomy 8
5q-
5q-, komplex
Normal karyotype
Bone marrow blasts
t
Patterns of Evolution in MDS, n= 46 Patienten (according to Tricot et al., 1984), own modification
P53 ?
![Page 11: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/11.jpg)
G-C
CC
G
-CC
C
Genetic Evolution of MDS
AML
Bone marrow blasts
t
Patterns of Evolution in MDS, n= 46 Patienten (according to Tricot et al., 1984), own modification
?
CD34 FISH
![Page 12: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/12.jpg)
G-C
CC
G
-CC
C
CD34-FISH
• Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood, 1995, Leukemia, 1997)
• Increased number of circulating CD34+ progenitor cells in peripheral blood in MDS patients (Vehmeyer et al. Leuk. Res., 2001)
• Circulating CD34+ cells can be enriched from peripheral blood by immunomagnetic cell sorting (MACS®)
• Most chromosomal aberrations found by banding procedures can also be identified by FISH
• FISH analyses can be performed on enriched circulating CD34+ cells
Background
![Page 13: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/13.jpg)
G-C
CC
G
-CC
C
CD34-FISH The Method
• 20-30 ml peripheral blood
• Immunomagnetic Cell Sorting of CD34+ cells (MACS®)
• 80 000 – 400 000 CD34+ cells/sample
• FISH analyses
Braulke et al., Leuk Res 2010
![Page 14: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/14.jpg)
G-C
CC
G
-CC
C
CD34-FISH The Pilot Study
Braulke et al., Leuk Res 2010
Analysing circulating CD34+ cells by FISH…
• is a reliable method to survey the size of an aberrant clone in peripheral blood
• works in high-risk as well as in low-risk MDS
• is representative for the clonal situation in the bone marrow
• allows a very frequent monitoring during therapy
• may reduce the need for repeated bone marrow biopsies
• helps in all cases where a bone marrow biopsy is not possible or unsuccessful
• n=27 pts. with MDS • n=16 pts. with higher risk MDS and at least 4 cycles of 5-Aza
![Page 15: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/15.jpg)
G-C
CC
G
-CC
C
CD34-FISH
Super-panel
Initial screening
M2
M4
M6
M8
M10 M 12 Mo
24 M 21
M18
M15
Superpanel Standardpanel Standardpanel
1. year follow-up 2. year follow-up
Super-panel
M30
M27
M33
Mo 36
3. year follow-up
Super-panel
Standardpanel
Superpanel: 12 probes: D7/CEP7, EGR1/D5, CEP8, CEP X/Y, D20, TP53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p/1q, CSF1R
Standardpanel: 7 probes: EGR1/D5, D7/CEP7, CEP8, TP53, D20, TEL/AML1, CEP X/Y
• Bone marrow biopsies every 6-12 months (recommendation)
• Peripheral blood counts once a month
• Full blood counts at time points of FISH analyses
Design of the Study
Multicentric German prospective CD34 FISH Study
![Page 16: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/16.jpg)
G-C
CC
G
-CC
C
CD34-FISH Interim Study Results:
Patients n=389
• Participating Centers n=18 • Male: female 1.15: 1.0 • Median age 70.5 years (40-90) • Median time of follow-up 8.2 Months (1 – 36) • LeMon5-Study n=110 • AZALE-Study n=25
38%
72%
Cytogenetics by CD34 FISH from pB (all pts.)
normal
aberrant
61% 18%
8% 9%
2 1
Frequencies of aberrations
Pat. mit 1 Anomalie
Pat. mit 2 Anomalien Pat. mit 3 Anomalien Pat. mit 4 Anomalien Pat. mit 5 Anomalien
45% 55%
Cytogenetics by CD34 FISH from pB (without AZALE/LeMon5)
normal aberrant
![Page 17: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/17.jpg)
G-C
CC
G
-CC
C
CD34-FISH Interim Study Results:
• Karyotype evolution detected in ~13% of pts. as yet
(median observation time of 9 months)
• Confirmation of evolution patterns known by CBA
• Delineation of new evolution patterns
![Page 18: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/18.jpg)
G-C
CC
G
-CC
C
Combining FISH and SNP Analysis of CD34+ blood cells
Aims: • To increase number of informative cases
• To improve diagnostic accuracy
![Page 19: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/19.jpg)
G-C
CC
G
-CC
C
Array
Affymetrix CytoScan HD Array
2.6 million markers – 750.000 SNPs – 1.800.000 CNV
100% of known cancer genes (526)
average marker spacing: 1,148 bp
250 ng DNA (own exp.: 100 ng possible)
3-4 days
![Page 20: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/20.jpg)
G-C
CC
G
-CC
C
Pilot Study • N= 23 pts. • SNP-analysis of CD34+ blood cells (n=23) • Chromosome banding analysis of bm aspirate (n=22), pb (n=1) • FISH-analysis of CD34+ blood cells (n=21), bm (n=2) • Diagnoses: MDS: n=20, AML: n=3
• Results: # of abnormalities detected depending on the method
Conclusion:
•SNP + FISH on CD34+ pb feasible
•SNP-A increases the number of detectable abnormalities
num
ber o
f pat
ient
s
number of abnormalities
![Page 21: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/21.jpg)
G-C
CC
G
-CC
C
Case Report 1
• Gain of genetic information
• Proof of clonality
![Page 22: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/22.jpg)
G-C
CC
G
-CC
C
Case Report 1 • Suspected MDS RCMD, normal karyotype
TET2 Polymor-phism
• Proof of a microdeletion in 4q14 containing the TET2-gene (size 0.8 Mb) and a polymorphic deletion of 0.2 Mb proof of clonality
![Page 23: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/23.jpg)
G-C
CC
G
-CC
C
Case Report 2
• Gain of genetic information
• Improvement of prognostication
![Page 24: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/24.jpg)
G-C
CC
G
-CC
C
Case Report 2 (MDS RAEB-II)
• Karyotype: 47,XY,+8 [18]/46,XY [7]
• FISH-analysis of CD34+ blood cells: • +8 in 56 % of
interphase nuclei
![Page 25: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/25.jpg)
G-C
CC
G
-CC
C
Case Report 2 (MDS-RAEB-II)
Consequence: • Worse prognosis with +8
and additional UPD 7q
UPD (7)(q11qter)
CD34+ bm cells
![Page 26: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/26.jpg)
G-C
CC
G
-CC
C
Case Report 3
• Gain of genetic information
• Dissection of the molecular anatomy of a ring chromosome 11
![Page 27: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/27.jpg)
G-C
CC
Case Report 3: Secondary AML after MDS Karyotype: 46,XX,del(5)(q13q33),r(11)hsr(11)(q23)
![Page 28: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/28.jpg)
G-C
CC
• FISH-analysis of CD34+ blood cells: • 5q- in 98 % of interphase
nuclei
• MLL amplification in 93%
of interphase nuclei
Karyotype: 46,XX,del(5)(q13q33),r(11)hsr(11)(q23)
EGR (5q31) D5S23, D5S721 (5p15.2)
MLL telomeric MLL centromeric
![Page 29: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/29.jpg)
G-C
CC
G
-CC
C
Combining FISH and SNP Analysis of CD34+ blood cells
diploid
amplification
deletion
Delineation of the molecular anatomy of a ring chromosome 11 with different regions of closely connected small deletions and amplifications of different degrees (3x - >10x) („chromotrypsis“) this case has complex abnormalities: prognosis: intermediate very poor
MLL
Dissection of ringchromosome 11
![Page 30: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/30.jpg)
G-C
CC
G
-CC
C
Combined Sequential FISH + SNP-Study
“Sequential comprehensive genetic analysis of circulating CD 34+ cells in MDS” Start: Spring 2013
Observation period
24 months
MDS, low- and int-1 according to IPSS,
n= 75 pts, Enrollment period: 12 months
Cytogenetic analysis of peripheral blood cells
every three months
CD34+FISH-analyis
Cytogenetic analysis of bone marrow cells
according to guidelines
CD34+SNP-array-analysis
Chromosomal banding analysis
![Page 31: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/31.jpg)
G-C
CC
U
nive
rsitä
tsK
rebs
zent
rum
G
-CC
C
Göt
tinge
n
Com
preh
ensi
ve C
ance
r Cen
ter
Acknowledgements CD34 FISH- project: F. Braulke Cytogenetics/FISH/24 colour FISH: K. Shirneshan SNP-Array-Analysis/ CD34 FISH + SNP- project: C. Ganster Cytogenetic Prognosis: J. Schanz Lab technicians: R. Steffens, C. Schütze, C. Schulte, A. Kaufmann, S. Raimer-Probst, A.-K. Künzel, M. Neu, C. Wachenhausen, A. Tsetoulidis, A. Kominowski, B. M. Wendt, A. Gutermuth
International collaborators: F. Solé, M. Mallo, Barcelona G. Mufti, A. Mohamedali, London H. Tuechler, Vienna CD34 FISH Study members: M. Metz Göttingen J. Seraphin, S. Detken Northeim K. Götze, C. Müller-Thomas München U. Platzbecker Dresden T.H. Brümmendorf Aachen U. Germing, A. Kündgen Düsseldorf G. Bug, O. Ottmann Frankfurt A. Giagounidis Duisburg W.-K. Hofmann, F. Nolte Mannheim A. Böhme Frankfurt P. Schafhausen, J. Isernhagen Hamburg K. Jentsch-Ullrich Magdeburg B. Schmidt München M. Lübbert Freiburg R.F. Schlenk Ulm W. Blau Berlin
![Page 32: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/32.jpg)
G-C
CC
G
-CC
C
Reserve slides
![Page 33: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/33.jpg)
G-C
CC
G
-CC
C
Do we enrich enough cells for FISH + SNP?
26 MDS patients
3*105 cells -> 600 ng DNA
1*105 cells -> 200 ng DNA
Leucocyte count (pb) before enrichment Leuc
ocyt
e co
unts
afte
r im
mun
omag
netic
e
nric
hmen
t of C
D34+
cel
ls
![Page 34: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/34.jpg)
G-C
CC
Karyotype evolution by CB and CD34+ pb FISH-Analysis
FISH-Analysis of CD34+ pb: − 5q- − -7 − TEL-loss (12p-) − TP53-loss (17p-) − 20q- − RB1-loss (13q-)
EGR1 D5S721
D7S522 (7q31) CEP7
RB1
ISCN-Karyotype: 44,XX,del(5)(q13q33),-7,del(12)(p13p11.2),-17,- der(17;20)(q10;p10) [23]/ 44,idem,der(3;6)(p10;q10) [2]
![Page 35: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/35.jpg)
G-C
CC
Karyotype evolution by SNP-Analysis (CD34+ pb)
Month 0:
Loss UPD
ISCN-Karyotype: 44,XX,del(5)(q13q33),-7,del(12)(p13p11.2),-17,der(17;20)(q10;p10) [23]/ 44,idem,der(3;6)(p10;q10) [2]
![Page 36: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/36.jpg)
G-C
CC
Karyotype evolution by SNP-Analysis (CD34+ pb)
Month 0:
Loss UPD
ISCN-Karyotype: 44,XX,del(5)(q13q33),-7,del(12)(p13p11.2),-17,der(17;20)(q10;p10) [23]/ 44,idem,der(3;6)(p10;q10) [2]
Evolution (Month 4): additional loss regression of 13q-
![Page 37: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/37.jpg)
Sponsored by:
Participating Experts:
Detlef Haase, M.D., Ph.D. University of Göttingen Germany
Stuart Schwartz, Ph.D. Labcorp Research Triangle Park, NC
Brought to you by the Science/AAAS Custom Publishing Office
Webinar Series Science
30 January 2013
Genetic Biomarkers Revealed: Unraveling the Complexities of Cancer Genomes in Blood Malignancies
![Page 38: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/38.jpg)
UTILIZATION OF A SNP MICROARRAY FOR THE STUDY
OF LEUKEMIA
STUART SCHWARTZ, PHD, FACMG
Wednesday, January 30, 2013 12:00 P.M.
![Page 39: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/39.jpg)
I am an employee of Laboratory
Corporation of America Holdings®
DISCLOSURE
![Page 40: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/40.jpg)
VALIDATION AND CLINICAL STUDIES
• CLL - >225 patients • MDS - >800 patients • Others - >200 patients
• CMML, AML, ALL, MM and Tumors
• Will focus on CLL and MDS today • What will array analysis add to the evaluation
of these patients [INTERNAL DATA – DECEMBER, 2012]
![Page 41: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/41.jpg)
Platform currently utilized in laboratory
More than 2.69 million markers ◦ Across the entire genome (spacing ~384 bp in ISCA genes)
743,304 SNPs (single nucleotide polymorphisms) ◦ Polymorphic probes ◦ Assessing copy number changes ◦ Assessing genotypes
1,953,246 structural probes (copy number probes) ◦ Non-polymorphic ◦ Assessing copy number change
AFFYMETRIX® SNP CYTOSCANTM HD
![Page 42: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/42.jpg)
MDS STUDIES
NORMAL CHROMOSOME – ARRAY FINDINGS
ABNROMAL CHROMOSOMES/FISH – ARRAY ADDITIONAL INFORMATION
![Page 43: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/43.jpg)
CYTOGENETIC ABNORMALITIES
50%
NORMAL 35%
ARRAY ONLY ABNORMALITIES
15%
INITIAL MDS STUDY– %ABNORMALITIES
30% OF NORMAL CHROMOSOME FINDINGS – ARRAY ABNORMALITY
![Page 44: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/44.jpg)
NORMAL CHROMOSOMES/FISH ARRAY – DETECTED RUNX1 DELETIONS
![Page 45: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/45.jpg)
PATIENT FINDINGS - IMPLICATIONS
Normal cytogenetics Patients ~1-2.6 Mb deletion of 21q22.11-q22.12
– Includes RUNX1 Implications of RUNX1 deletion
– Predictor of poor overall survival – Patients have an inferior event free survival – Resistance to therapy and inferior outcome
Only detected by array analysis
![Page 46: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/46.jpg)
CLINICAL STUDY - MDS
Utilization of microarray for the routine study of patients to evaluate MDS
>800 patients studied Results Overall, when chromosomes were normal
Array studies revealed an additional 24.3% of patients with abnormalities
When chromosomes were abnormal, Array provided additional information in 40% - of the time Prognostic information in 36% of the patients obtained
![Page 47: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/47.jpg)
CLINICAL STUDY - MDS
Results When both flow cytometry and hematopathology
evaluation could not definitively confirm MDS Array analysis - abnormalities in 27.4% of the patients
When either flow cytometry and hematopathology evaluation were consistent with MDS Array analysis revealed abnormalities in 80% of the patients
51.5% of the patients with abnormalities in this study had segmental UPD The majority (54.9%) were as individual changes 39.2% were present with copy number change
![Page 48: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/48.jpg)
CLINICAL STUDY - MDS
Results Clonal evolution was seen in 21.2% of the patients Chromothripsis in 6.1% of patients
The most common changes seen involved the TET2 gene (either as a deletion of
UPD4q – 19.2% of patients, RUNX1 gene involved ~7.0%
![Page 49: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/49.jpg)
MDS – (20q-) PATIENT STUDY ADDITIONAL INFORMATION
68 year old Initial diagnosis – persistent pancytopenia of unclear
etiology Flow analysis – no abnormalities Cytogenetic/FISH findings
Cytogenetic – 46,XY,del(20)(q11.2q13.3)[5]/46,XY[15] FISH – 20q- (2.8% of cells)
![Page 50: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/50.jpg)
20Q DELETION DETECTED BY THE ARRAY ~15% OF DNA
![Page 51: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/51.jpg)
CHROMOSOME 14 UPD; DISTAL ~75%; PROXIMAL 15%; UPD 14 – INITIAL ABNORMALITY; 20Q- CLONAL EVOLUTION
![Page 52: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/52.jpg)
ARRAY - SIGNIFICANCE
Array findings Deletion 20q confirmed Uniparental 14 detected
Uniparental disomy Associated with homozygous mutation UPD 14 – shown to be the initial abnormality (driver of
disease) Clonal evolution detected
Deletion 20q Expansion of UPD
![Page 53: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/53.jpg)
CLL STUDIES
NORMAL CHROMOSOME – ARRAY FINDINGS
ABNROMAL CHROMOSOMES/FISH – ARRAY ADDITIONAL INFORMATION
![Page 54: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/54.jpg)
CLL PATIENT STUDY – NORMAL FISH
Patient with CLL No abnormality detected from routine FISH analysis
Array – duplication of 2p – Marker of progression and indicative of poor
prognosis – Not detected by targeted analysis
Acquired uniparental disomy (UPD) 17 – Suggestive of homozygous p53 mutation – Detectable by a SNP array
![Page 55: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/55.jpg)
CLL – BETTER DELINEATION BY ARRAY ANALYSIS
64 year old male Flow: antigenic profile characteristic of chronic
lymphocytic leukemia (CLL) ~30% of total CD38 expression – not detected ZAP70 expression – not detected FISH: Only 13q deletion (72.5%) These are all better prognostic factors
![Page 56: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/56.jpg)
13q- INCLUDING RB1 AND MIR15/16
![Page 57: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/57.jpg)
SEGMENTAL UPD FOR 17P DETECTED
![Page 58: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/58.jpg)
ARRAY ANALYSIS
Array analysis demonstrated three abnormalities 13q deletion (includes Rb1 and mir15/16) - ~55% 11p deletion - ~55% aUPD 17p - ~80%
Segmental UPD of 17p – predominant finding Findings suggest association with an
adverse prognosis
![Page 59: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/59.jpg)
CLL PATIENT – GENOME COMPLEXITY
89 year old male FISH Trisomy 12 13q deletion
Flow: 89% of leukocytes with a B-cell chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) phenotype
Morphology – consistent with CLL/SLL
![Page 60: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/60.jpg)
CHROMOSOME 13 – GENOME INSTABILITY NUMEROUS DELETIONS - CHROMOSOMTHRIPSIS
![Page 61: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/61.jpg)
NO GAIN OR LOSS OF GENETIC MATERIAL UPD – 19Q
![Page 62: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/62.jpg)
CLL PATIENT – GENOME COMPEXITY
FISH findings Intermediate
But array Complex lymphoid evolution Two clones
100% and 85%
Chromothripsis Uniparental disomy Genome complexity
![Page 63: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/63.jpg)
24 of 25 patients had normal chromosome findings 21 of 24 had abnormalities by the array (87.5%)
7 (of 25) patients had both normal chromosomes and FISH 4 of 7 had abnormalities by the array (57.1%)
18 (of 25) patients had abnormalities by chromosomes/FISH All (100%) had additional abnormalities detected by
the array
MULTIPLE MYELOMA – RESULTS OVERVIEW
![Page 64: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/64.jpg)
MULTIPLE MYELOMA – CCND1+
5 patients Normal karyotypes FISH – Extra signal CCND1+
Based on FISH – Trisomy 11/Hyperdiploid Better prognosis?
Based on array Two patients – Hyperdiploid; better prognosis Three patients – Unfavorable prognosis
![Page 65: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/65.jpg)
![Page 66: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/66.jpg)
MULTIPLE MYELOMA – CCND1+
Array reveals complex abnormalities Hyperdiploid Multiple gains and loss
1p- and 8q+ (MYC)
Chromothripsis Multiple gains and losses Chromosomes 1 and 12
Uniparental disomy Chromosomes 13 and 16
Overall Unfavorable prognosis
![Page 67: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/67.jpg)
ACQUIRED UPD
Segmental UPD – important and prevalent in a variety of leukemias
Over 120 patients with UPD identified Seen overall in ~15% of patients
40% - CMML 45.5% - Tumors
Seen as isolated anomaly ~54% of the time Majority was segmental and could be detected with
as little as 10% DNA
![Page 68: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/68.jpg)
ACQUIRED UPD - IMPLICATIONS
• Important and frequent finding in cancer • Only detectable with genotyping array • In some patients associated with poor course • Most common aUPD regions seen in MDS: 4q, 9p,
11q, 17p • Thought to provide mechanism to duplicate existing
mutation • In TET2, JAK2, CBL,TP53, respectively
![Page 69: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/69.jpg)
Advantages Delineation of all abnormalities in the genome
Clear demarcation of breakpoints – genes involved
Detection of: Uniparental disomy Homozygous deletions Chromothripsis
Detection of abnormalities not available by FISH and not seen in chromosome analysis
Ability to better provide better prognostic information
BENEFITS OF ARRAY
![Page 70: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/70.jpg)
Disadvantages Cannot pick up balanced translocations Mosaicism – FISH more sensitive than array
However – have been able to detect 7% mosaicism Close to sensitivity of FISH
ARRAY - DISADVANTAGES
![Page 71: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/71.jpg)
DIAGNOSTIC/PROGNOSTIC
As discussed initially – array provides additional information – which can be used for better prognosis
Prognostic/diagnostic information obtained by SNP array in a variety of cancers CLL (Abnormal) - 32.2% MDS - 37.1%
![Page 72: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/72.jpg)
OVERALL IMPLICATIONS
Microarray should be used in any leukemia (CLL, MDS, AML, ALL or solid tumor) when cytogenetics and FISH are normal – For both prognosis and diagnosis
Microarray can be used in abnormal patients with CLL and MDS to better define prognosis Also – AML, ALL, CML
Only SNP array can detected UPD
![Page 73: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/73.jpg)
CONCLUSIONS
Detects both copy number and copy neutral changes Detection of abnormalities in cytogenetics/FISH normal
patients Dosage levels correlate with progression/clonal evolution Resolve complex karyotypes, cryptic rearrangements Unidentifiable chromosomes Wrong assumptions
Detection of additional abnormalities in >60% of patients Detection of complexity Provides diagnostic/prognostic information
![Page 74: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/74.jpg)
ACKNOWLEDGEMENTS
LabCorp Peter Papenhausen Jim Tepperberg Inder Gadi Rachel Burnside Vikram Jaswaney Karen Phillips Hiba Risheg Liz Keitges Rao Potluri Romela Passion Brooke Rush Holly Taylor
LabCorp - Array Lab ◦ Mike Phelan ◦ Brian Williford ◦ Carolyn Bullen ◦ Jessica Whaley-Davis ◦ Renee Royster ◦ Laurelin Cottingham ◦ Colin Osborne ◦ Jeff Meitz ◦ Chris Younger ◦ Christina Goss ◦ Savanna Schepis
![Page 75: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/75.jpg)
Sponsored by:
Participating Experts:
Detlef Haase, M.D., Ph.D. University of Göttingen Germany
Stuart Schwartz, Ph.D. Labcorp Research Triangle Park, NC
Brought to you by the Science/AAAS Custom Publishing Office
To submit your questions, type them into the text box
and click .
Webinar Series Science
30 January 2013
Genetic Biomarkers Revealed: Unraveling the Complexities of Cancer Genomes in Blood Malignancies
![Page 76: PLEASE STAND BY… the webinar Genetic Biomarkers Revealed...G-CCC. CD34-FISH •Circulating CD34+ cells show the same chromosomal aberrations as bone marrow cells (Haase et al., Blood,](https://reader030.vdocuments.us/reader030/viewer/2022040411/5ed4f4c3554b1d277246339e/html5/thumbnails/76.jpg)
Look out for more webinars in the series at: webinar.sciencemag.org
For related information on this webinar topic, go to: www.affymetrix.com/cancer
To provide feedback on this webinar, please e-mail your comments to [email protected]
Sponsored by:
Brought to you by the Science/AAAS Custom Publishing Office Brought to you by the Science/AAAS Custom Publishing Office
Webinar Series Science
30 January 2013
Genetic Biomarkers Revealed: Unraveling the Complexities of Cancer Genomes in Blood Malignancies