ArticleCell cycle (Georgetown, Tex.)2014
Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Stratified Medicine Pediatrics: Cell-Free DNA and Serial Tumor Sequencing Identifies Subtype-Specific Cancer Evolution and Epigenetic States.Cancer discovery · 2025Article
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- Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene Panel Testing.Current issues in molecular biology · 2024Article
- A prognostic model based on DNA methylation-related gene expression for predicting overall survival in hepatocellular carcinoma.Frontiers in oncology · 2023Article
- Genomic Breakpoints' Characterization of a LargeDiagnostics (Basel, Switzerland) · 2022Article
- Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy.JNCI cancer spectrum · 2022Article
- A comprehensive analysis of somatic alterations in Chinese ovarian cancer patients.Scientific reports · 2021Article
- Loss of CHEK2 Predicts Progression in Stage pT1 Non-Muscle-Invasive Bladder Cancer (NMIBC).Pathology oncology research : POR · 2020Article
- Criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for the Classification of Germline Sequence Variants in Risk Genes for Hereditary Breast and Ovarian Cancer.Geburtshilfe und Frauenheilkunde · 2020Article
- Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test?International journal of molecular sciences · 2020Review
- HLA-G 3' untranslated region variants +3187G/G, +3196G/G and +3035T define diametrical clinical status and disease outcome in epithelial ovarian cancer.Scientific reports · 2019Article
- Article
- Bioinformatics and Drug Discovery.Current topics in medicinal chemistry · 2017Review
- Big genomics and clinical data analytics strategies for precision cancer prognosis.Scientific reports · 2016Article
- Targeting SOD1 induces synthetic lethal killing in BLM- and CHEK2-deficient colorectal cancer cells.Oncotarget · 2015Article
- Mutated Fanconi anemia pathway in non-Fanconi anemia cancers.Oncotarget · 2015Article
- The BRCA1/2-directed miRNA signature predicts a good prognosis in ovarian cancer patients with wild-type BRCA1/2.Oncotarget · 2015Article
- Adverse Drug Events-based Tumor Stratification for Ovarian Cancer Patients Receiving Platinum Therapy.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2015Article
- Hereditary ovarian cancer: not only BRCA 1 and 2 genes.BioMed research international · 2015Review
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-grade serous ovarian cancer (HG-SOC), a major histologic type of epithelial ovarian cancer (EOC), is a poorly-characterized, heterogeneous and lethal disease where somatic mutations of TP53 are common and inherited loss-of-function mutations in BRCA1/2 predispose to cancer in 9.5-13% of EOC patients. However, the overall burden of disease due to either inherited or sporadic mutations is not known. We performed bioinformatics analyses of mutational and clinical data of 334 HG-SOC tumor samples from The Cancer Genome Atlas to identify novel tumor-driving mutations, survival-significant patient subgroups and tumor subtypes potentially driven by either hereditary or sporadic factors. We identified a sub-cluster of high-frequency mutations in 22 patients and 58 genes associated with DNA damage repair, apoptosis and cell cycle. Mutations of CHEK2, observed with the highest intensity, were associated with poor therapy response and overall survival (OS) of these patients (P = 8.00e-05), possibly due to detrimental effect of mutations at the nuclear localization signal. A 21-gene mutational prognostic signature significantly stratifies patients into relatively low or high-risk subgroups with 5-y OS of 37% or 6%, respectively (P = 7.31e-08). Further analysis of these genes and high-risk subgroup revealed 2 distinct classes of tumors characterized by either germline mutations of genes such as CHEK2, RPS6KA2 and MLL4, or somatic mutations of other genes in the signature. Our results could provide improvement in prediction and clinical management of HG-SOC, facilitate our understanding of this complex disease, guide the design of targeted therapeutics and improve screening efforts to identify women at high-risk of hereditary ovarian cancers distinct from those associated with BRCA1/2 mutations.
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