Genome-Wide Copy Number Alteration Profiles in Various Ovarian Carcinomas
TL Mao, HL Kao, JJ Sheu, KT Kuo. National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Chinese Medical Science, Taichung, Taiwan
Background: Ovarian carcinoma consists of several different types as defined by WHO, namely serous, endometrioid, clear cell, mucinous and transitional cell. Based on morphological features and molecular studies of ovarian carcinomas, dualistic pathogenetic pathways had been proposed and classified into low grade and high grade. High-throughput methods including expression profiling, comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array had been applied in an effort to search tumor suppressor genes and oncogenes in ovarian carcinoma. However, the results varied in different studies and the comparison among different types of ovarian carcinoma is not comprehensive.
Design: In this study, we compared the genome-wide copy number alterations among different types of ovarian carcinomas, including 9 high-grade serous carcinomas (HG), 13 endometrioid carcinomas (EM), 9 clear cell carcinomas (CC) and 5 transitional cell carcinomas (TC). High-resolution SNP array (250K) was performed using affinity-purified samples (>95% purity) from fresh specimens. The data was analyzed using dChip 2006 software. Probesets with an inferred log2 ratio > 0.3 or < -0.3 were classified as gain and loss, respectively. LOH analysis was carried out by the HMM-based method, using 60 normal human samples for reference genotypes.
Results: Among the four types of ovarian carcinoma analyzed, HG and TCC had the highest level of copy number alterations whereas CCC had the lowest level of copy number alterations. LOH is also most frequent in HG and TCC, while CCC and EM had relatively fewer LOH events. Amplification of Ch 1q is most frequent and is unique in EM. Amplification of 8q is most frequent in CCC and less common in other types of ovarian carcinoma. Candidate genes within the minimal amplicons include ZBTB10, KLF10 and AZIN1. Another specific region of amplification most common in CCC resides in Ch 20q, in which TPD52 and ZNF217 are candidate genes amplified. For HG and TCC, similar patterns of amplification of Ch 3q, 10p and deletion of Ch 3p, 5q and 8p were observed.
Conclusions: Our result demonstrated distinct patterns of copy number alterations in different types of ovarian carcinoma. CCC had the lowest level of copy number alterations, while HG and TCC had the highest level of copy number alterations. Interestingly, HG and TCC had similar molecular profiles, suggesting the wide morphological spectrum within a molecularly unique type of carcinoma.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 164, Wednesday Afternoon