ZNF217 Gene Amplification and PIK3CA Mutation Are Associated with Ovarian Clear Cell Carcinoma
KT Kuo, TL Mao, N Jinawath, RJ Kurman, TL Wang, IM Shih. National Taiwan University Hospital, Taipei, Taiwan; Johns Hopkins Medical Institutions, Baltimore, MD
Background: Ovarian clear cell carcinomas (CCC) are histologically unique among different types of primary ovarian carcinomas but it is unknown if the molecular genetic signatures of CCC are different from other common types of ovarian cancer.
Design: A total of 89 ovarian CCC were studied for their molecular genetic alterations. We employed a high resolution (250K) single nucleotide polymorphism (SNP) array analysis on 12 CCC for which the tumor cells were affinity purified from fresh specimens to avoid potential stromal cell contamination and culture artifacts. The chromosomal instability (CIN) level in CCC was compared to high-grade (HG) and low-grade (HG) ovarian serous carcinomas. An additional 77 cases of CCC were used for mutation analysis of KRAS, BRAF, PIK3CA, and CTNNB1 (b-catenin).
Results: The overall chromosomal instability level in CCC reflected by DNA copy number changes was similar to LG serous carcinomas but was significantly lower than HG serous carcinomas. Amplification of chr20q13 was detected in 5 of 12 cases based on analyzing SNP array data but rarely in HG and none in LG serous carcinomas. This 20q13 amplicon contains at least one candidate oncogene, ZNF217, which has been shown to participate in oncogenesis in several types of human cancer including ovarian carcinoma. Mutation analysis demonstrated somatic sequence mutations of PIK3CA, KRAS, CTNNB1 (b-catenin) and BRAF in 28 (31.5%), 7 (7.9%), 3 (3.4%) and 0 of 89 CCC cases, respectively.
Conclusions: Our current findings in combination with previously published data suggest that the molecular genetic changes in ovarian CCC are distinct among ovarian surface epithelial neoplasms. The table below shows the relative frequency of molecular genetic changes in different types of ovarian carcinomas.
EMC: ovarian endometrioid carcinoma; MUC: mucinous carcinoma; NK: not known, ***: frequently present; *: rarely present; -: not present based on published studies.
|CIN level||TP53||PIK3CA mutation||KRAS mutation||BRAF mutation||CTNNB1 mutation||ZNF217 amplicon|
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 150, Wednesday Morning