ArticleDiseases of the colon and rectum2019
Detection of Pathogenic Germline Variants Among Patients With Advanced Colorectal Cancer Undergoing Tumor Genomic Profiling for Precision Medicine.
Article in Diseases of the colon and rectum, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2023Guideline
- A systematic literature review of disclosure practices and reported outcomes for medically actionable genomic secondary findings.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Pooled it
- The Landscape of Genomic and Socioeconomic Variables in Patients with Colorectal Cancer Based on Genetic Ancestry.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive 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
- Decoding the Genetic Landscape of Postoperative Nausea and Vomiting in Cancer Surgery: A New Frontier in Personalized Medicine Driven by Genome-Wide Association Studies.Indian journal of surgical oncology · 2025Review
- Prognostic Significance of the Comprehensive Biomarker Analysis in Colorectal Cancer.Life (Basel, Switzerland) · 2025Review
- Establishment of a comprehensive set of fact sheets for cancer predisposition genes for medical oncologists practicing cancer genome profiling.International journal of clinical oncology · 2025Review
- Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy.Cancer cell international · 2024Review
- Limited Independent Follow-Up with Germline Testing of Variants Detected inJournal of immunotherapy and precision oncology · 2024Article
- Review
- Young-onset colorectal cancer.Nature reviews. Disease primers · 2023Review
- Comprehensive Analysis of Early-onset Colorectal Cancer: A Review.Journal of the anus, rectum and colon · 2023Review
- Incidental germline findings during molecular profiling of tumor tissues for precision oncology: molecular survey and methodological obstacles.Journal of translational medicine · 2022Article
- Homologous Recombination Deficiency in Ovarian, Breast, Colorectal, Pancreatic, Non-Small Cell Lung and Prostate Cancers, and the Mechanisms of Resistance to PARP Inhibitors.Frontiers in oncology · 2022Review
- MCM9 is associated with germline predisposition to early-onset cancer-clinical evidence.NPJ genomic medicine · 2021Article
- Identification of theJCO global oncology · 2021Article
- Review
- First report of a Mexican family with mutation in the CDH1 gene.Molecular genetics & genomic medicine · 2020Article
- Dominantly Inherited Hereditary Nonpolyposis Colorectal Cancer Not Caused by MMR Genes.Journal of clinical medicine · 2020Review
- Evolving Significance of Tumor-Normal Sequencing in Cancer Care.Trends in cancer · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGenomic profiling of colorectal cancer aims to identify actionable somatic mutations but can also discover incidental germline findings.
objectiveThe purpose of this study was to report the detection of pathogenic germline variants that confer heritable cancer predisposition.
designThis was a retrospective study. SETTINGS: The study was conducted at a tertiary-referral institution. PATIENTS: Between 2012 and 2015, 1000 patients with advanced cancer underwent targeted exome sequencing of a 202-gene panel. The subgroup of 151 patients with advanced colorectal cancer who underwent matched tumor-normal (blood) sequencing formed our study cohort.
interventionsGermline variants in 46 genes associated with hereditary cancer predisposition were classified according to a defined algorithm based on in silico predictions of pathogenicity. Patients with presumed pathogenic variants were examined for type of mutation, as well as clinical, pedigree, and clinical genetic testing data.
main outcome measuresWe measured detection of pathogenic germline variants.
resultsA total of 1910 distinct germline variants were observed in 151 patients. After filtering, 15 pathogenic germline variants (9.9%) were found in 15 patients, arising from 9 genes of varying penetrance for colorectal cancer (APC (n = 2; 13%), ATM (n = 1; 6%), BRCA1 (n = 2; 13%), CDH1 (n = 2; 13%), CHEK2 (n = 4; 27%), MSH2 (n = 1; 7%), MSH6 (n = 1; 7%), NF2 (n = 1; 7%), and TP53 (n = 1; 7%)). Patients with pathogenic variants were diagnosed at a younger age than those without (median, 45 vs 52 y; p = 0.03). Of the 15 patients, 7 patients (46.7%) with variants in low/moderate- penetrant genes for colorectal cancer would likely have not been tested based on clinical and pedigree criteria, where 2 harbored clinically actionable variants (CDH1 and NF2, 28.5% of 7). LIMITATIONS: This study was limited by its small sample size and advanced-stage patients.
conclusionsTumor-normal sequencing can incidentally discover clinically unsuspected germline variants that confer cancer predisposition in 9.9% of patients with advanced colorectal cancer. Precision medicine should integrate clinical cancer genetics to inform and interpret the actionability of germline variants and to provide follow-up care to mutation carriers. See Video Abstract at http://links.lww.com/DCR/A906.
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