ArticleHuman molecular genetics2022
Frequency of pathogenic germline variants in cancer susceptibility genes in 1336 renal cell carcinoma cases.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- ERN GENTURIS clinical practice guidelines for the diagnosis, surveillance and management of people with Birt-Hogg-Dubé syndrome.European journal of human genetics : EJHG · 2024Guideline
- Characteristics, aetiology and implications for management of multiple primary renal tumours: a systematic review.European journal of human genetics : EJHG · 2024Pooled it
- Hereditary kidney tumor syndromes: structured evaluation of a questionnaire-based approach.Clinical kidney journal · 2026Article
- MITF (p.E318K) and renal cell carcinoma: current evidence does not support an effect.Journal of medical genetics · 2026Article
- Insights from 2057 germline genetic tests in renal cell carcinoma patients support revisiting testing criteria.European journal of human genetics : EJHG · 2026Article
- Clinical and genetic features of multiple primary tumours cohorts with a renal cell carcinoma: Implications for molecular genetic investigations.International journal of cancer · 2025Article
- Genetic Testing and Counselling for Hereditary Renal Carcinoma: What Do Clinicians Need to Know?European urology open science · 2025Review
- Age-specific familial risks in cancer as clues to germline genetic and environmental causes: focus on colorectal, endometrial, prostate, kidney, breast and lung cancers.Hereditary cancer in clinical practice · 2025Review
- The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project.British journal of cancer · 2024Article
- Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study.The Journal of urology · 2024Article
- Article
- Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.Nature communications · 2024Article
- Cancer Survivorship Care in the United States at Facilities Accredited by the Commission on Cancer.JAMA network open · 2024Article
- Integrative Analysis of Germline Rare Variants in Clear and Non-clear Cell Renal Cell Carcinoma.European urology open science · 2024Article
- Hereditary Renal Cancer Syndromes.Medical sciences (Basel, Switzerland) · 2024Review
- Clonal Evolution in Healthy and Premalignant Tissues: Implications for Early Cancer Interception Strategies.Cancer prevention research (Philadelphia, Pa.) · 2023Review
- Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma.Translational andrology and urology · 2023Article
- AtypicalFrontiers in oncology · 2023Article
- Differences in Cancer Phenotypes Among Frequent CHEK2 Variants and Implications for Clinical Care-Checking CHEK2.JAMA oncology · 2022Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Renal cell carcinoma (RCC) occurs in a number of cancer predisposition syndromes, but the genetic architecture of susceptibility to RCC is not well defined. We investigated the frequency of pathogenic and likely pathogenic (P/LP) germline variants in cancer susceptibility genes (CSGs) within a large series of unselected RCC participants. Whole-genome sequencing data on 1336 RCC participants and 5834 controls recruited to the UK 100 000 Genomes Project, a nationwide multicentre study, was analyzed to identify rare P/LP short variants (single nucleotide variants and insertions/deletions ranging from 1 to 50 base pairs) and structural variants in 121 CSGs. Among 1336 RCC participants [mean: 61.3 years (±12 SD), range: 13-88 years; 64% male], 85 participants [6.4%; 95% CI (5.1, 7.8)] had one or more P/LP germline variant in a wider range of CSGs than previously recognized. A further 64 intragenic variants in CSGs previously associated with RCC were classified as a variant of uncertain significance (VUS) (24 'hot VUSs') and were considered to be of potential clinical relevance as further evaluation might results in their reclassification. Most patients with P variants in well-established CSGs known to predispose to renal cell carcinoma (RCC-CSGs) were aged <50 years. Burden test analysis for filtered variants in CSGs demonstrated a significant excess of CHEK2 variants in European RCC participants compared with the healthy European controls (P = 0.0019). Approximately, 6% of the patients with RCC unselected for family history have a germline variant requiring additional follow-up analysis. To improve diagnostic yield, we suggest expanding the panel of RCC-CSGs tested to include CHEK2 and all SDHx subunits and raising the eligibility criteria for age-based testing.
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