DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma
Journal
Clinical Cancer Research
Journal Volume
16
Journal Issue
7
Pages
1997-2008
Date Issued
2010
Author(s)
Chen X.
Feng Y.
Nakayama K.
Wang Y.
Glas R.
Ma M.J.
Kurman R.J.
Shih I.-M.
Wang T.-L.
Abstract
Purpose: 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 PIK3CA. The purpose of this study is to comprehensively define the genomic changes in CCC based on DNA copy number alterations. Experimental Design: 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. Results: 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 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 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. Conclusions: 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. ?2010 AACR.
SDGs
Other Subjects
DNA; small interfering RNA; article; cancer cell culture; cancer staging; cancer therapy; chromosomal instability; chromosome 20; clear cell carcinoma; controlled study; gene amplification; gene deletion; gene locus; gene mutation; genome; growth inhibition; heterozygosity loss; human; human tissue; molecular genetics; oncogene; ovary carcinoma; PIK3CA gene; priority journal; real time polymerase chain reaction; single nucleotide polymorphism; znf217 gene; Adenocarcinoma, Clear Cell; Cell Line, Tumor; Chromatography, Affinity; Chromosomal Instability; DNA Copy Number Variations; DNA, Neoplasm; Female; Gene Dosage; Gene Expression Profiling; Genome-Wide Association Study; Humans; Microarray Analysis; Ovarian Neoplasms; Polymorphism, Single Nucleotide; Trans-Activators
Type
journal article