Kim Yong-Man, Lee Shin-Wha, Chun Sung-Min, Kim Dae-Yeon, Kim Jong-Hyeok, Kim Kyu-Rae, Kim Young-Tak, Nam Joo-Hyun, van Hummelen Paul, MacConaill Laura E, Hahn William C, Jang Se Jin
Department of Obstetrics & Gynecology, University of Ulsan, ASAN Medical Center, Seoul, Korea; ASAN Center for Cancer Genome Discovery, ASAN Medical Center, Seoul, Korea.
Department of Pathology, University of Ulsan, ASAN Medical Center, Seoul, Korea; ASAN Center for Cancer Genome Discovery, ASAN Medical Center, Seoul, Korea.
PLoS One. 2014 Jun 17;9(6):e99451. doi: 10.1371/journal.pone.0099451. eCollection 2014.
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.
癌症基因组图谱（TCGA）的一项研究已证明TP53突变在卵巢癌中占主导地位。然而，初始治疗后复发性卵巢癌的分子特征一直未得到充分评估。本研究旨在使用OncoMap突变检测方案，调查原发性和复发性上皮性卵巢癌配对样本中的体细胞点突变模式。我们采用了一种高通量基因分型平台来确定一大组已知癌症基因的突变状态。使用OncoMap v.4.4评估从92个福尔马林固定、石蜡包埋（FFPE）肿瘤中分离的基因组DNA，这些肿瘤由46例上皮性卵巢癌（EOC）患者的初始诊断肿瘤和复发性肿瘤的配对样本组成。在33.7%的样本中观察到突变，其中29.3%的样本有单个突变，其余4.3%有两个或更多突变。在分析的41个基因中，在四个基因中发现了35个突变，即CDKN2A（2.2%）、KRAS（6.5%）、MLH1（8.2%）和TP53（20.7%）。TP53是最常发生突变的基因，但任何基因的突变与临床预后之间均无相关性。此外，原发性和复发性卵巢癌之间的体细胞突变没有差异。复发性样本中出现的每个突变在相应的原发性样本中均被检测到。总之，这些韩国EOC样本的OncoMap数据表明，在CDKN2A、KRAS、MLH1和TP53中发现了体细胞突变。未检测到原发性和复发性样本之间的突变状态差异。为了解上皮性卵巢癌肿瘤复发的生物学机制，需要进行更多研究，包括表观遗传修饰或其他基因的额外突变。
