Work

Genetic similarity between cancers and comorbid Mendelian diseases identifies candidate driver genes

Year: 2015

Type: article

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. Historically, Mendelian disorders were used to provide the first insight into cancer-associated genes. Here Melamed et al.use the unprecedented scope of electronic health records to explore genetic relationships and uncover potentially new drivers of cancer.

Source: Nature Communications

DOI: 10.1038/ncomms8033

Authors: Rachel D. Melamed, Kevin J. Emmett, Chioma Madubata, Andrey Rzhetsky, Raul Rabadan

Institutions: Columbia University, University of Chicago

Language: English

Topic: Cancer Genomics and Diagnostics

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990