ArticleBMC medical genetics2018
Identification of genetic variants for clinical management of familial colorectal tumors.
Article in BMC medical genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- A Novel Detection Method for High-Order SNP Epistatic Interactions Based on Explicit-Encoding-Based Multitasking Harmony Search.Interdisciplinary sciences, computational life sciences · 2024Article
- Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families.Acta neuropathologica communications · 2023Article
- Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer.The Kaohsiung journal of medical sciences · 2023Article
- Article
- Review
- MLH1 intronic variants mapping to + 5 position of splice donor sites lead to deleterious effects on RNA splicing.Familial cancer · 2020Article
- Broadening risk profile in familial colorectal cancer type X; increased risk for five cancer types in the national Danish cohort.BMC cancer · 2020Article
- Prevalence of CNV-neutral structural genomic rearrangements in MLH1, MSH2, and PMS2 not detectable in routine NGS diagnostics.Familial cancer · 2020Article
- Association Study ofPharmacogenomics and personalized medicine · 2020Article
- Novel candidates in early-onset familial colorectal cancer.Familial cancer · 2020Article
- New Pathogenic Germline Variants in Very Early Onset and Familial Colorectal Cancer Patients.Frontiers in genetics · 2020Article
- Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing.Scientific reports · 2019Article
- From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.International journal of cancer · 2019Review
- Genetics, diagnosis and treatment of Lynch syndrome: Old lessons and current challenges.Oncology letters · 2019Review
- Germline Pathogenic Variants in Homologous Recombination and DNA Repair Genes in an Asian Cohort of Young-Onset Colorectal Cancer.JNCI cancer spectrum · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe genetic mechanisms for families who meet the clinical criteria for Lynch syndrome (LS) but do not carry pathogenic variants in the mismatch repair (MMR) genes are still undetermined. We aimed to study the potential contribution of genes other than MMR genes to the biological and clinical characteristics of Norwegian families fulfilling Amsterdam (AMS) criteria or revised Bethesda guidelines.
methodsThe Hereditary Cancer Biobank of the Norwegian Radium Hospital was interrogated to identify individuals with a high risk of developing colorectal cancer (CRC) for whom no pathogenic variants in MMR genes had been found in routine diagnostic DNA sequencing. Forty-four cancer susceptibility genes were selected and analyzed by using our in-house designed TruSeq amplicon-based assay for targeted sequencing. RNA splicing- and protein-dedicated in silico analyses were performed for all variants of unknown significance (VUS). Variants predicted as likely to affect splicing were experimentally analyzed by resorting to minigene assays.
resultsWe identified a patient who met the revised Bethesda guidelines and carried a likely pathogenic variant in CHEK2 (c.470 T > C, p.I157T). In addition, 25 unique VUS were identified in 18 individuals, of which 2 exonic variants (MAP3K1 c.764A > G and NOTCH3 c.5854G >A) were analyzed in the minigene splicing assay and found not to have an effect on RNA splicing.
conclusionsAmong high-risk CRC patients that fulfill the AMS criteria or revised Bethesda guidelines, targeted gene sequencing identified likely pathogenic variant and VUS in other genes than the MMR genes (CHEK2, NOTCH3 and MAP3K1). Our study suggests that the analysis of genes currently excluded from routine molecular diagnostic screens may confer cancer susceptibility.
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