Department of Gynecology, Longgang District Maternity and Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China.
Department of Cell Biology and Medical Genetics, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, China.
J Cell Mol Med. 2023 Nov;27(21):3259-3270. doi: 10.1111/jcmm.17893. Epub 2023 Jul 31.
Epithelial ovarian cancer (EOC) is one of the most prevalent gynaecological cancers worldwide. The molecular mechanisms of serous ovarian cancer (SOC) remain unclear and not well understood. SOC cases are primarily diagnosed at the late stage, resulting in a poor prognosis. Advances in molecular biology techniques allow us to obtain a better understanding of precise molecular mechanisms and to identify the chromosome instability region and key driver genes in the carcinogenesis and progression of SOC. Whole-exome sequencing was performed on the normal ovarian cell line IOSE80 and the EOC cell lines SKOV3 and A2780. The single-nucleotide variation burden, distribution, frequency and signature followed the known ovarian mutation profiles, without chromosomal bias. Recurrently mutated ovarian cancer driver genes, including LRP1B, KMT2A, ARID1A, KMT2C and ATRX were also found in two cell lines. The genome distribution of copy number alterations was found by copy number variation (CNV) analysis, including amplification of 17q12 and 4p16.1 and deletion of 10q23.33. The CNVs of MED1, GRB7 and MIEN1 located at 17q12 were found to be correlated with the overall survival of SOC patients (MED1: p = 0.028, GRB7: p = 0.0048, MIEN1: p = 0.0051), and the expression of the three driver genes in the ovarian cell line IOSE80 and EOC cell lines SKOV3 and A2780 was confirmed by western blot and cell immunohistochemistry.
上皮性卵巢癌（EOC）是全球最常见的妇科癌症之一。浆液性卵巢癌（SOC）的分子机制仍不清楚，也未被充分理解。SOC 病例主要在晚期诊断，预后较差。分子生物学技术的进步使我们能够更好地了解精确的分子机制，并确定 SOC 发生和发展过程中的染色体不稳定性区域和关键驱动基因。对正常卵巢细胞系 IOSE80 和 EOC 细胞系 SKOV3 和 A2780 进行了全外显子组测序。单核苷酸变异负担、分布、频率和特征遵循已知的卵巢突变图谱，没有染色体偏向。在两种细胞系中还发现了复发性突变的卵巢癌驱动基因，包括 LRP1B、KMT2A、ARID1A、KMT2C 和 ATRX。通过拷贝数变异（CNV）分析发现了基因组拷贝数改变的分布，包括 17q12 和 4p16.1 的扩增和 10q23.33 的缺失。位于 17q12 的 MED1、GRB7 和 MIEN1 的 CNV 与 SOC 患者的总生存相关（MED1：p=0.028，GRB7：p=0.0048，MIEN1：p=0.0051），并通过western blot 和细胞免疫组化证实了这三个驱动基因在卵巢细胞系 IOSE80 和 EOC 细胞系 SKOV3 和 A2780 中的表达。
