Cancer Cytogenetics

Diagnostic and Prognostic Significance

Diane C. Arthur, M.D.

Head, Clinical Cytogenetics Section

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

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

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

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 NIAID in particular).

Clinical applications
Our research is highly collaborative and clinical. Results of our tests are currently used for diagnosis, patient entry onto research protocols, assignment to particular treatment regimens, monitoring response to therapy, and correlation with outcome.

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 tumors Discover 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

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, MET Steven Holland NIAID Katherine Calvo CC, DLM, Hematology Thomas Uldrick NCI, CCR, HAMB Steven Pavletic NCI, CCR, ETIB Dennis Hickstein NCI, CCR, ETIB

Extramural
Susana Raimondi St. Jude Childrens Research Hospital Michelle LeBeau University of Chicago LoAnn Peterson Northwestern University