ArticleNature communications2015
Genetic similarity between cancers and comorbid Mendelian diseases identifies candidate driver genes.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Shared genetics between breast cancer and predisposing diseases identifies novel breast cancer treatment candidates.Research square · 2024Article
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- LeMeDISCO is a computational method for large-scale prediction & molecular interpretation of disease comorbidity.Communications biology · 2022Article
- Integrating Multimorbidity into a Whole-Body Understanding of Disease Using Spatial Genomics.Results and problems in cell differentiation · 2022Article
- A global overview of genetically interpretable multimorbidities among common diseases in the UK Biobank.Genome medicine · 2021Article
- MendelVar: gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes.Bioinformatics (Oxford, England) · 2021Article
- High incidence ofTherapeutic advances in medical oncology · 2020Article
- Comorbidity of asthma and hypertension may be mediated by shared genetic dysregulation and drug side effects.Scientific reports · 2019Article
- Novel disease syndromes unveiled by integrative multiscale network analysis of diseases sharing molecular effectors and comorbidities.BMC medical genomics · 2018Article
- Reforming disease classification system-are we there yet?Annals of translational medicine · 2018Article
- Article
- Mendelian Disease Associations Reveal Novel Insights into Inflammatory Bowel Disease.Inflammatory bowel diseases · 2018Article
- The ribosomal protein gene RPL5 is a haploinsufficient tumor suppressor in multiple cancer types.Oncotarget · 2017Article
- Identification of disease comorbidity through hidden molecular mechanisms.Scientific reports · 2016Article
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5 authors.
Funding
Abstract
Despite large-scale cancer genomics studies, key somatic mutations driving cancer, and their functional roles, remain elusive. Here, we propose that analysis of comorbidities of Mendelian diseases with cancers provides a novel, systematic way to discover new cancer genes. If germline genetic variation in Mendelian loci predisposes bearers to common cancers, the same loci may harbour cancer-associated somatic variation. Compilations of clinical records spanning over 100 million patients provide an unprecedented opportunity to assess clinical associations between Mendelian diseases and cancers. We systematically compare these comorbidities against recurrent somatic mutations from more than 5,000 patients across many cancers. Using multiple measures of genetic similarity, we show that a Mendelian disease and comorbid cancer indeed have genetic alterations of significant functional similarity. This result provides a basis to identify candidate drivers in cancers including melanoma and glioblastoma. Some Mendelian diseases demonstrate 'pan-cancer' comorbidity and shared genetics across cancers.
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