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Cancer Cytogenetics

Diagnostic and PrognosticSignificance

Diane C. Arthur, M.D.

Head, Clinical Cytogenetics Section

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Research Expertise and Methods

Areas of expertise

Clinical cytogenetics, including both constitutional and acquired

chromosome abnormalities

Identification and interpretation of cytogenetic abnormalities in

hematologic malignancies and pediatric solid tumors

Methods, technologies, approaches

Tissue culture tailored to patient diagnosis (blood, bone marrow,

solid tissues)

Full G-banded karyotype analysis

Interphase and metaphase fluorescence in-situ hybridization

(FISH)

Collaborative clinical research

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Ongoing Collaborative Research Projects

Intramural

Diagnostic and prognostic significance of cytogenetic abnormalities in

Inherited bone marrow failure syndromes

Chronic lymphocytic leukemia

Multiple myeloma, smoldering myeloma

Immunodeficiency associated with GATA2 mutations

Primary effusion lymphoma

Patients undergoing bone marrow transplantation for

hematologic malignancies

Extramural

American Society of Hematology, National Cancer Institute, and

Agrupacion Mexicana para el Estudio de la Hematologia A.C.

Cooperative Mexican Cytogenetics Laboratory Standardization

Project

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Examples / Data / Results From Research Area

Interphase FISH for Classification and Treatment Assignment in B-CLL

TP53 deletion: High risk disease, BTK inhibitor therapy ATM deletion: Young age, marked lymphadenopathy,

high risk disease, intensive therapy indicated

Trisomy 12: Intermediate risk, standard therapy 13q14.3 deletion: Low risk disease, watch and wait

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Research Implications

Within and outside LP

Our clinical cytogenetics studies are an integral part of investigations

focusing on hematolymphoid malignancies within the LP

(Hematopathology, Flow Cytometry, Molecular Pathology) and the

broader NIH community (NCI, DLM Hematology, NHLBI, and NIAIDin particular).

Clinical applications

Our research is highly collaborative and clinical. Results of our tests

are currently used for diagnosis, patient entry onto researchprotocols, assignment to particular treatment regimens, monitoring

response to therapy, and correlation with outcome.

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Future Direction

In the next 5-10 years we must

Resurrect SKY Spectral Karyotyping technology

Adopt new microarray technology

More completely characterize the molecular cytogenetic changes in

hematologic malignancies and possibly selected solid tumorsDiscover new molecular cytogenetic changes of potential diagnostic,

prognostic, and biological significance

Current challenges and obstacles

Limited numbers and types of patients

Access to fresh tissue

Acquiring the microarray technology and bioinformatic support

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Collaborators

Intramural

Blanche Alter NCI, DCEG, CGB

Neelam Giri NCI, DCEG, CGB

Irina Maric CC, DLM, Hematology

Adrian Wiestner NHLBI, HB

Maryalice Stetler-Stevenson NCI, CCR, LP

Ola Landgren NCI, CCR, METSteven Holland NIAID

Katherine Calvo CC, DLM, Hematology

Thomas Uldrick NCI, CCR, HAMB

Steven Pavletic NCI, CCR, ETIB

Dennis Hickstein NCI, CCR, ETIB

Extramural

Susana RaimondiSt. Jude Childrens Research Hospital

Michelle LeBeau University of Chicago

LoAnn Peterson Northwestern University