Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 125, Issue 10, Pages 2342-2348Publisher
WILEY
DOI: 10.1002/ijc.24642
Keywords
RCC; SNP; LOH; telomere length
Categories
Funding
- NCI [CA098997]
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The identification of genetic aberrations may help understand file mechanisms of tumorigenesis and has important implications in diagnosis, prognosis and treatment. We applied Illumina's 317K high-density single nucleotide polymorphism (SNP) arrays to profile chromosomal aberrations in clear cell renal cell carcinoma (ccRCC) from 80 patients and analyzed the association of LOH/amplification events with clinicopathological characteristics and telomere length. The most common loss of heterozygosity (LOH) were 3D (69 cases) including 38 whole 3p arm losses. 30 large fragment LOH (spanning 3p21-36)., and I interstitial LOH (spanning 3p12-14, 3p21-22, 3p24.1-24.2 and 3p24.3). followed by chromosome losses at 8p12-pter, 6q23.3-27, 14q24.1-qter, 9q32-qter, 10q22.3-qter. 9p13.3-pter, 4q28.3-qter and 13q12.1-21.1. We also found several smallest overlapping regions of LOH that contained tumor suppressor genes. One smallest LOH in 8p12 had a size of 0.29 Mb and only contained one gene (NRGI). The most frequent chromosome gains were at 5q (32 cases), including 10 whole 5q amplification, 21 large amplifications encompassing 5q32-ter and focal amplification in 5q35.3 (0.42 Mb). The other common chromosome gains were 1q25.1-qter. 7q21.13-qter, 8q24.12-qter and whole 7p arm. Significant associations of LOH at 9p, 9q, 14q and 18q were observed with higher nuclear grade. Significant associations with tumor stage were observed for LOH at 14q, 18p and 21q. Finally. we found that tumors with LOH at 2q, 6p, 6q, 9p, 9q and 17p had significantly shorter telomere length than those without LOH. This is the first study to use Illumina's SNP-CGH array that provides a close estimate of the size and frequency of chromosome LOH and amplifications of ccRCC. The identified regions and genes may become diagnostic and prognostic biomarkers as well as potential targets of therapy. (C) 2009 UICC
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