Chang Ohk Sung1, In-Hye Song2, Insuk Sohn3. 1. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: co.sung@amc.seoul.kr. 2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Samsung Cancer Research Institute, Seoul, Republic of Korea. Electronic address: insuks@gmail.com.
Abstract
OBJECTIVE: High-grade serous ovarian cancer (HGS-OvCa), the most common epithelial ovarian cancer, is very complex and heterogeneous at the molecular level. The identification of intrinsic HGS-OvCa subgroups characterized by specific molecular alterations and aggressive behavior could improve patient treatment. METHODS: High-resolution copy number data for 560 HGS-OvCa patients and gene expression data obtained from the TCGA database were analyzed to identify distinct molecular subgroups based on significant focal somatic copy number alterations (SCNAs). RESULTS: Using unsupervised consensus clustering, a subgroup accounting for 26.8% of the patients (150/560 patients) characterized by focal somatic copy number amplification at chromosome 19 was identified. The subgroup was independently associated by multivariate Cox regression analysis with poor overall (HR, 1.61; P = 0.001) and progression-free survival (HR, 1.36; P = 0.036). The specific focal SCNA locations were 19p13.2, 19p13.12, 19p13.11, 19q12, 19q13.12, and 19q13.2. The differential gene expression signature of the subgroup compared with that of the remaining patients also suggested that chromosome 19 was the mainly amplified region. The clinical significances of subgroup 2 were validated in independent data sets using the gene expression signature characteristics. In addition, the subgroup had a tendency toward mutual exclusivity with patients with BRCA1/2 mutations. The most significantly altered pathway of the subgroup was the cyclin and cell cycle regulation pathway. CONCLUSION: A unique molecular subgroup associated with poor survival was identified based on focal SCNAs and could aid the further molecular classification of ovarian cancers.
OBJECTIVE: High-grade serous ovarian cancer (HGS-OvCa), the most common epithelial ovarian cancer, is very complex and heterogeneous at the molecular level. The identification of intrinsic HGS-OvCa subgroups characterized by specific molecular alterations and aggressive behavior could improve patient treatment. METHODS: High-resolution copy number data for 560 HGS-OvCa patients and gene expression data obtained from the TCGA database were analyzed to identify distinct molecular subgroups based on significant focal somatic copy number alterations (SCNAs). RESULTS: Using unsupervised consensus clustering, a subgroup accounting for 26.8% of the patients (150/560 patients) characterized by focal somatic copy number amplification at chromosome 19 was identified. The subgroup was independently associated by multivariate Cox regression analysis with poor overall (HR, 1.61; P = 0.001) and progression-free survival (HR, 1.36; P = 0.036). The specific focal SCNA locations were 19p13.2, 19p13.12, 19p13.11, 19q12, 19q13.12, and 19q13.2. The differential gene expression signature of the subgroup compared with that of the remaining patients also suggested that chromosome 19 was the mainly amplified region. The clinical significances of subgroup 2 were validated in independent data sets using the gene expression signature characteristics. In addition, the subgroup had a tendency toward mutual exclusivity with patients with BRCA1/2 mutations. The most significantly altered pathway of the subgroup was the cyclin and cell cycle regulation pathway. CONCLUSION: A unique molecular subgroup associated with poor survival was identified based on focal SCNAs and could aid the further molecular classification of ovarian cancers.
Authors: Elisabet Einarsdottir; Lena Hafrén; Eira Leinonen; Mahmood F Bhutta; Erna Kentala; Juha Kere; Petri S Mattila Journal: Sci Rep Date: 2016-09-16 Impact factor: 4.379
Authors: Garrett W Rhyasen; Yi Yao; Jingwen Zhang; Austin Dulak; Lillian Castriotta; Kelly Jacques; Wei Zhao; Farzin Gharahdaghi; Maureen M Hattersley; Paul D Lyne; Edwin Clark; Michael Zinda; Stephen E Fawell; Gordon B Mills; Huawei Chen Journal: PLoS One Date: 2018-07-23 Impact factor: 3.240