DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma.
OBJECTIVE
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.


METHODS
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.
Division of Gynecological Pathology, Departments of Pathology, Gynecology/Obstetrics, and Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kuan-Ting
KT
Kuo
Tsui-Lien
TL
Mao
Xu
X
Chen
Yuanjian
Y
Feng
Kentaro
K
Nakayama
Yue
Y
Wang
Ruth
R
Glas
M Joe
MJ
Ma
Robert J
RJ
Kurman
Ie-Ming
IeM
Shih
Tian-Li
TL
Wang
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity / Q000379:methods*; D043171:Chromosomal Instability; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000032:analysis / Q000302:isolation & purification*; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D046228:Microarray Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D015534:Trans-Activators / Q000235:genetics
D004273:DNA, Neoplasm; D015534:Trans-Activators; C113698:ZNF217 protein, human