Copy number variations and loss of heterozygosity identified in myelodysplastic syndrome

s 471 Chromosomal microarray as a clinical tool for 13q14 deletion subtyping in chronic lymphocytic leukemia Shelly Gunn , Karine Hovanes , Michelle N. Strecker , Xavier Reveles , Rashmi Shah , Lony Lim a CombiMatrix Diagnostics, Irvine, CA, USA; START Center for Cancer Care, San Antonio, TX, USA Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease which has proven amenable to subtyping through genomic microarray analysis. Initially, 13q14 deletions as an isolated finding were associated with a favorable prognosis. However, recent evidence has revealed significant heterogeneity within the 13q14 deletion subtype, thus, there is a clear clinical need for more precise stratification of 13q14 deletions at the genomic level. The minimal deleted region (MDR) includes: DLEU2, DLEU7, MIR15A/MIR16-1 and part of DLEU1. Recent studies suggest that in addition to the MDR, the size of the deletion and the involvement of the nearby tumor suppressor gene RB1 serve as an independent prognostic biomarker for disease progression. Nine individuals in whom a 13q deletion had previously been identified by bacterial artificial chromosome (BAC) array were re-analyzed using the Cancer Cytogenomics Microarray Consortium’s consensus design on an Agilent (Santa Clara, CA) 180K oligonucleotide platform. Based on the size and location of the 13q14 deletion, cases were further classified as having type (smaller, not including RB1) or type II (larger, including RB1) deletions, as described by Ouilette et al. (Cancer Res, 2008). Type I deletions were seen in 77% of cases, and Type II deletions in 22%. There was a single case of a biallelic 13q14 deletion. Deleted regions ranged in size from 1.0 to 9.8 Mb. Unlike older BAC technologies that are subject to limited resolution, the CCMC 180K oligonucleotide array allowed for further clarification of 13q deletion cases, providing valuable clinical and prognostic information for CLL. Conflict of Interest: Dr. Gunn is the medical director at Combimatrix Diagnostics. Copy number variations and loss of heterozygosity identified in myelodysplastic syndrome X. Hu , A. Iqbal , A. Ahmed , G. Raca , X. Xu , D.J. Wolff , R. Burack , D. Mulford , M.M. Li a Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA; University of Wisconsin-Madison, WI, USA; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid neoplasms with high risk of progression to acute myeloid leukemia (AML). The molecular pathogenic mechanisms that underlie the transformation of MDS to AML are largely unknown. About 50% of MDS patients show no cytogenetic abnormalities, making monitoring disease progress in these patients difficult. We hypothesize that some cryptic genomic copy number variations (CNVs) and regions with copy number neutral loss of heterozygosity (CN-LOH) may be or harbor genetic events responsible for the disease transformation. We studied 80 patients with newly diagnosed MDS to evaluate genomic alterations using a custom designed cancer specific CGH microarray that targets over 500 cancer genes and more than 100 cancer-associated genomic regions. Thirty six MDS cases were studied for CN-LOH using a SNP array or a combined CGH/SNP array platform that detects both CNVs and CN-LOH. CNVs were identified in all patients including 38 patients with normal cytogenetic results. The CNVs were enriched in genomic regions containing cancer genes TP73, CSF1R, NOTCH1, AKT1, BLM, and BUB1B. Twenty-five of the 36 MDS cases showed CN-LOH of 10Mb in 63 genomic regions. Although CN-LOH was distributed throughout the whole genome, 1p and 14q were more frequently involved. These results demonstrate the utility of arrays that detect both CNVs and CN-LOH in cancer analysis. Our study revealed many previously unrecognized CNVs and CN-LOH in patients with MDS, which may play important roles in the transformation of MDS to AML and be or contain biomarkers for cancer diagnosis and/or appropriate targeted therapies. Conflict of Interest: Some of the arrays used in this study were provided by Agilent Technologies.