Publication Date:
2012-11-16
Description:
Abstract 2531 DNA repair and repair-related genes encode molecules that function as critical guardians of the genome, both in terms of chromosome stability and single base integrity. Defects in such functions, both inherited and acquired, represent key factors that contribute to the etiology of cancer (e.g., RB1, TP53 and ATM). Copy number alterations (CNAs) in such genes have been described for one or more hematologic malignancies and disease-specific testing is routinely employed for the detection of these important diagnostic/prognostic markers. Additional DNA repair genes have been implicated as potential factors influencing the onset, progression, and/or chemo-resistance of disease. In the present study, we analyzed 155 DNA repair/repair-related genes for CNAs in 425 cases of hematologic malignancy using microarray analysis. Cases represented nine distinct clinical entities with at least 30 cases per entity. Disorders represented include myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), myeloproliferative neoplasm (MPN), chronic myeloid leukemia (CML), B-cell and T-cell acute lymphoblastic leukemia (B-ALL, T-ALL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). An oligo-based microarray platform was employed with higher density coverage for the DNA repair/ repair-related genes (1 probe/0.2–7.0 kb). Results were assessed relative to multiple databases of known benign variation. A proof of principal analysis included RB1, TP53 and ATM, for which genomic alterations and disease preference have been well established. Analysis of RB1 revealed CNAs in 74 cases (4 gains and 70 losses) (17.4% of total) with copy gains uniformly attributable to trisomy 13 in cases of B-ALL. As expected, loss of RB1 typically reflected either monosomy 13 (31/70 seen predominately in MM) or smaller deletions (∼1 Mb, seen in CLL). CNAs in TP53 included 2 gains and 42 losses (10.4% of total), with gains again related to trisomy (exclusively hyperdiploid B-ALL), whereas deletions varied in size and disease association. CNAs in the ATM included 28 gains and 19 losses (11.1% of total). Gains reflecting trisomy correlated with diverse diagnoses, while more focal gains (∼10 Mb) were seen exclusively in B-ALL (3 cases). Not surprisingly, small losses of ATM (
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink