DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma.
DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma.
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DOI：
10.1158/1078-0432.ccr-09-2105
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Wang TL
中科院分区：
文献类型：
--
作者：
Kuo KT;Mao TL;Chen X;Feng Y;Nakayama K;Wang Y;Glas R;Ma MJ;Kurman RJ;Shih IeM;Wang TL
Advanced ovarian clear cell carcinoma (CCC) is one of the most malignant 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 PIK3CA. The purpose of this study is to comprehensively define the genomic changes in CCC based on DNA copy number alterations. We performed 250K high-density SNP 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. 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, ZNF217. This is observed in 36% of CCCs but rarely detected in serous carcinomas regardless of grade. In addition, homozygous deletions are detected at CDKN2A/2B and LZTS1 loci. Interestingly, the DNA copy number changes observed in fresh CCC tissues are rarely detected in the established CCC cell lines. 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.
