Abstract

<div>Abstract<p><b>Purpose:</b> Advanced ovarian clear cell carcinoma (CCC) is one of the most aggressive ovarian malignancies, in part because it tends to be resistant to platinum-based chemotherapy. At present, little is known about the molecular genetic alterations in CCCs except that there are frequent activating mutations in <i>PIK3CA</i>. The purpose of this study is to comprehensively define the genomic changes in CCC based on DNA copy number alterations.</p><p><b>Experimental Design:</b> We performed 250K high-density single nucleotide polymorphism array analysis in 12 affinity-purified CCCs and 10 CCC cell lines. Discrete regions of amplification and deletion were also analyzed in additional 21 affinity-purified CCCs using quantitative real-time PCR.</p><p><b>Results:</b> The level of chromosomal instability in CCC as defined by the extent of DNA copy number changes is similar to those previously reported in low-grade ovarian serous carcinoma but much less than those in high-grade serous carcinoma. The most remarkable region with DNA copy number gain is at chr20, which harbors a potential oncogene, <i>ZNF217</i>. This discrete amplicon is observed in 36% of CCCs but rarely detected in serous carcinomas regardless of grade. In addition, homozygous deletions are detected at the <i>CDKN2A/2B</i> and <i>LZTS1</i> loci. Interestingly, the DNA copy number changes observed in fresh CCC tissues are rarely detected in the established CCC cell lines.</p><p><b>Conclusions:</b> This study provides the first high resolution, genome-wide view of DNA copy number alterations in ovarian CCC. The findings provide a genomic landscape for future studies aimed at elucidating the pathogenesis and developing new target-based therapies for CCCs. Clin Cancer Res; 16(7); 1997–2008. ©2010 AACR.</p></div>

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