ArticleNature communications2018
Systematic discovery of germline cancer predisposition genes through the identification of somatic second hits.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review.BMC cancer · 2019Pooled it
- Widespread Epistasis between Cancer Driver Mutations and Allele-Specific Copy Number Variations.bioRxiv : the preprint server for biology · 2025Article
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- Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations.Nature communications · 2024Article
- Systematic analysis of Mendelian disease-associated gene variants reveals new classes of cancer-predisposing genes.Genome medicine · 2023Article
- Comprehensive genomic profiling of breast cancers characterizes germline-somatic mutation interactions mediating therapeutic vulnerabilities.Cell discovery · 2023Article
- Clonal Evolution in Healthy and Premalignant Tissues: Implications for Early Cancer Interception Strategies.Cancer prevention research (Philadelphia, Pa.) · 2023Review
- The impact of rare germline variants on human somatic mutation processes.Nature communications · 2022Article
- Mutational signatures are markers of drug sensitivity of cancer cells.Nature communications · 2022Article
- Article
- Gain of Chromosome 6p Correlates with Severe Anaplasia, Cellular Hyperchromasia, and Extraocular Spread of Retinoblastoma.Ophthalmology science · 2022Article
- Potential Involvement ofCancers · 2022Article
- Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers.Nature communications · 2021Article
- A protein interaction landscape of breast cancer.Science (New York, N.Y.) · 2021Article
- NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer.Life (Basel, Switzerland) · 2021Review
- X-CNV: genome-wide prediction of the pathogenicity of copy number variations.Genome medicine · 2021Article
- Prevalence of cancer susceptibility variants in patients with multiple Lynch syndrome related cancers.Scientific reports · 2021Article
- Clinical Quality in Cancer Research: Strategy to Assess Data Integrity of Germline Variants Inferred from Tumor-Only Testing Sequencing Data.Pharmaceutical medicine · 2021Article
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- Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
The genetic causes of cancer include both somatic mutations and inherited germline variants. Large-scale tumor sequencing has revolutionized the identification of somatic driver alterations but has had limited impact on the identification of cancer predisposition genes (CPGs). Here we present a statistical method, ALFRED, that tests Knudson's two-hit hypothesis to systematically identify CPGs from cancer genome data. Applied to ~10,000 tumor exomes the approach identifies known and putative CPGs - including the chromatin modifier NSD1 - that contribute to cancer through a combination of rare germline variants and somatic loss-of-heterozygosity (LOH). Rare germline variants in these genes contribute substantially to cancer risk, including to ~14% of ovarian carcinomas, ~7% of breast tumors, ~4% of uterine corpus endometrial carcinomas, and to a median of 2% of tumors across 17 cancer types.
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Registered trials
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