ArticleNature genetics2021
The context-specific role of germline pathogenicity in tumorigenesis.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Somatic mutations in Middle East and North Africa breast cancer patients: a systematic review.The oncologist · 2025Pooled it
- Management of individuals with germline pathogenic/likely pathogenic variants in CHEK2: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2023Guideline
- Article
- Sequencing approaches in hereditary cancer testing: strengths, limitations and future directions.European journal of human genetics : EJHG · 2026Review
- Why are Some Tissues More Vulnerable? Revisiting Tissue Specificity in Hereditary Cancer Syndromes.Molecular diagnosis & therapy · 2026Review
- Cancer type-specific variation in patterns of driver alterations across 50,000 tumors.Cancer cell · 2026Article
- Article
- Homologous recombination deficiency and hemizygosity drive resistance in breast cancer.Nature · 2026Article
- Universal Germline Genetic Testing in a Precision Oncology and Rare Cancer Clinic: Implementation and Outcomes.JCO oncology advances · 2026Article
- Age-related genomic characterization and therapeutic targets in Chinese breast cancer: insights from prospective targeted sequencing and clinical data analysis.BMC medicine · 2026Article
- Multiple myeloma risk linked to DNA damage response genes.Journal of hematology & oncology · 2026Article
- Landscape of germline genetic alterations among non-western young male patients with cancer. Findings from The Jordanian exploratory cancer genetics study.Frontiers in oncology · 2026Article
- The genetics of cancer heterogeneity and mesothelioma.Frontiers in oncology · 2026Review
- GATES: A Lightweight Tool Automating Pathogenic Variant Discovery From Raw Whole-Exome Sequencing Data.Cancer informatics · 2026Article
- Decoding Breast Cancer: Emerging Molecular Biomarkers and Novel Therapeutic Targets for Precision Medicine.International journal of molecular sciences · 2025Review
- Germline rare variants in cancer susceptibility genes and subsequent neoplasm risk after childhood cancer.Journal of the National Cancer Institute · 2025Article
- Severity of effect considerations regarding the use of mutation as a toxicological endpoint for risk assessment: A report from the 8th International Workshop on Genotoxicity Testing (IWGT).Environmental and molecular mutagenesis · 2025Review
- Germline variants of the POLH and RAD51 genes are candidate variants associated with risk of hormone receptor-negative young-onset breast cancer.NPJ breast cancer · 2025Article
- Using artificial intelligence (AI) to model clinical variant reporting for next generation sequencing (NGS) oncology assays.BioData mining · 2025Article
- Pathologist-initiated whole genome and transcriptome sequencing demonstrates diagnostic utility in resolving difficult-to-diagnose tumors.Genome medicine · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
38 authors.
Funding
Abstract
Human cancers arise from environmental, heritable and somatic factors, but how these mechanisms interact in tumorigenesis is poorly understood. Studying 17,152 prospectively sequenced patients with cancer, we identified pathogenic germline variants in cancer predisposition genes, and assessed their zygosity and co-occurring somatic alterations in the concomitant tumors. Two major routes to tumorigenesis were apparent. In carriers of pathogenic germline variants in high-penetrance genes (5.1% overall), lineage-dependent patterns of biallelic inactivation led to tumors exhibiting mechanism-specific somatic phenotypes and fewer additional somatic oncogenic drivers. Nevertheless, 27% of cancers in these patients, and most tumors in patients with pathogenic germline variants in lower-penetrance genes, lacked particular hallmarks of tumorigenesis associated with the germline allele. The dependence of tumors on pathogenic germline variants is variable and often dictated by both penetrance and lineage, a finding with implications for clinical management.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.