title: Analysis and comparison of somatic mutations in paired primary and recurrent epithelial ovarian cancer samples.
abstract: The TP53 mutations have been proved to be predominated in ovarian cancer in a study from The Cancer Genome Atlas (TCGA). However, the molecular characteristics of recurrent ovarian cancers following initial treatment have been poorly estimated. This study was to investigate the pattern of somatic point mutations in matched paired samples of primary and recurrent epithelial ovarian cancers, using the OncoMap mutation detection protocol. We have adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. OncoMap v.4.4 was used to evaluate genomic DNA isolated from a set of 92 formalin-fixed, paraffin-embedded (FFPE) tumors, consisting of matched paired samples of initially diagnosed and recurrent tumors from 46 epithelial ovarian cancer (EOC) patients. Mutations were observed in 33.7% of the samples, with 29.3% of these samples having a single mutation and the remaining 4.3% having two or more mutations. Among the 41 genes analyzed, 35 mutations were found in four genes, namely, CDKN2A (2.2%), KRAS (6.5%), MLH1 (8.2%) and TP53 (20.7%). TP53 was the most frequently mutated gene, but there was no correlation between the presence of mutation in any gene and clinical prognosis. Furthermore, somatic mutations did not differ between primary and recurrent ovarian carcinomas. Every mutation present in recurrent samples was detected in the corresponding primary sample. In conclusion, these OncoMap data of Korean EOC samples provide that somatic mutations were found in CDKN2A, KRAS, MLH1, and TP53. No differences in mutational status between primary and recurrent samples were detected. To understand the biology of tumor recurrence in epithelial ovarian cancer, more studies are necessary, including epigenetic modifications or additional mutations in other genes.
authors.affiliation: Department of Obstetrics & Gynecology, University of Ulsan, ASAN Medical Center, Seoul, Korea; ASAN Center for Cancer Genome Discovery, ASAN Medical Center, Seoul, Korea.
authors.forename: Yong-Man
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Obstetrics & Gynecology, University of Ulsan, ASAN Medical Center, Seoul, Korea; ASAN Center for Cancer Genome Discovery, ASAN Medical Center, Seoul, Korea.
authors.forename: Shin-Wha
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Ulsan, ASAN Medical Center, Seoul, Korea; ASAN Center for Cancer Genome Discovery, ASAN Medical Center, Seoul, Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Chun
authors.affiliation: Department of Obstetrics & Gynecology, University of Ulsan, ASAN Medical Center, Seoul, Korea.
authors.forename: Dae-Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Obstetrics & Gynecology, University of Ulsan, ASAN Medical Center, Seoul, Korea.
authors.forename: Jong-Hyeok
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, University of Ulsan, ASAN Medical Center, Seoul, Korea.
authors.forename: Kyu-Rae
authors.initials: KR
authors.lastname: Kim
authors.affiliation: Department of Obstetrics & Gynecology, University of Ulsan, ASAN Medical Center, Seoul, Korea.
authors.forename: Young-Tak
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Department of Obstetrics & Gynecology, University of Ulsan, ASAN Medical Center, Seoul, Korea.
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Nam
authors.affiliation: Center for Cancer Genome Discovery and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: van Hummelen
authors.affiliation: Center for Cancer Genome Discovery and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Laura E
authors.initials: LE
authors.lastname: MacConaill
authors.affiliation: Center for Cancer Genome Discovery and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.affiliation: Department of Pathology, University of Ulsan, ASAN Medical Center, Seoul, Korea; ASAN Center for Cancer Genome Discovery, ASAN Medical Center, Seoul, Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D009687:Nuclear Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019941:Cyclin-Dependent Kinase Inhibitor p16; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins