Atypical 11q Deletions Identified by Array CGH May Be Missed by FISH Panels for Prognostic Markers in Chronic Lymphocytic Leukemia
MC Mammarappallil, SR Gunn, MK Hibbard, M Lowery-Nordberg, EL Enriquez, ME Gorre, MS Mohammed, RS Robetorye. The University of Texas Health Science Center at San Antonio, San Antonio, TX; Clarient Diagnostics Laboratory, Aliso Viejo, CA; Louisiana State University Health Sciences Center, Shreveport, LA; Combimatrix Molecular Diagnostics, Irvine, CA
Background: Genomic alterations have increasingly gained importance as prognostic markers in chronic lymphocytic leukemia (CLL). The identification of genetic alterations of prognostic importance in CLL is currently accomplished using commercially available FISH panels that can detect the most common recurrent aberrations involving chromosomes 11q, 13q, 14q, 17p and whole chromosome 12. Although the use of FISH analysis has improved the detection rate of genomic alterations in CLL from approximately 50% using conventional cytogenetics to more than 80%, there is a need for improved methods to identify prognostic markers that can aid in the risk-stratification of these patients. Recently, array comparative genomic hybridization (array CGH) has been gaining acceptance as a diagnostic tool that can also be applied to detect genomic gains and losses of prognostic importance in CLL.
Design: Bacterial artificial chromosome array-based array GCH was used to detect recurrent genomic alterations in 190 cases of CLL using a clinically validated array designed to interrogate all known CLL prognostic loci.
Results: This analysis identified 22 CLL cases with 11q deletions, with 20 cases that included the ATM gene in the deleted region. However, three of the CLL cases showed atypical 11q deletions, with one case exhibiting a centromeric breakpoint just proximal to the ATM locus, and two cases exhibiting proximal breakpoints telomeric to the ATM gene. FISH analysis using an LSI ATM probe failed to detect the 11q deletions in all three CLL cases.
Conclusions: In the current study, we present three CLL cases with atypical 11q deletions that were not properly identified by a commercially available five probe FISH panel that included an 11q22 LSI ATM probe. This study is the first to report CLL cases with large 11q deletions that did not include the ATM gene, suggesting that additional genes in this region may be important for the pathogenesis of CLL. Although FISH analysis has contributed tremendously to the molecular cytogenetic understanding of the CLL genome, it is clear that many important genomic aberrations may be missed by currently available FISH prognostic marker panels.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 227, Tuesday Morning