title: A distinctive ovarian cancer molecular subgroup characterized by poor prognosis and somatic focal copy number amplifications at chromosome 19.
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.
  
  
  CONCLUSIONS
  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: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: co.sung@amc.seoul.kr.
authors: Chang Ohk
authors: CO
authors: Sung
authors: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: In-Hye
authors: IH
authors: Song
authors: Samsung Cancer Research Institute, Seoul, Republic of Korea. Electronic address: insuks@gmail.com.
authors: Insuk
authors: I
authors: Sohn
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D002888:Chromosomes, Human, Pair 19; D016000:Cluster Analysis; D018284:Cystadenocarcinoma, Serous / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: Carcinoma; Clustering; Copy number; Ovary; Prognosis; Serous