ArticleJCI insight2021
Germline mutations in a DNA repair pathway are associated with familial colorectal cancer.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Beyond Hematologic Malignancies: Colorectal Cancer as a Solid Tumor Manifestation of Inherited Bone Marrow Failure Syndromes.International journal of molecular sciences · 2025Review
- Andrographolide potentiates anti-tumor immunity in colorectal cancer (CRC) by targeting voltage-dependent anion channel (VDAC) and activating the cGAS-STING axis.Journal of gastrointestinal oncology · 2025Article
- Expression and clinical significance of FANCI gene in pan-cancer: a comprehensive analysis based on multi-omics data.Frontiers in genetics · 2025Article
- Integrating next-generation sequencing and artificial intelligence for the identification and validation of pathogenic variants in colorectal cancer.Frontiers in oncology · 2025Article
- Genomic alterations in two patients with esophageal carcinosarcoma identified by whole genome sequencing: a case report.Surgical case reports · 2024Article
- Article
- CRISPR/Cas9: a powerful tool in colorectal cancer research.Journal of experimental & clinical cancer research : CR · 2023Review
- Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma.Cancers · 2022Article
- A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.International journal of molecular sciences · 2022Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aiming to identify rare high-penetrance mutations in new genes for the underlying predisposition in familial colorectal cancer (CRC), we performed whole-exome sequencing in 24 familial CRCs. Mutations in genes that regulate DNA repair (RMI1, PALB2, FANCI) were identified that were related to the Fanconi anemia DNA repair pathway. In one pedigree, we found a nonsense mutation in CHEK2. CHEK2 played an essential role in cell cycle and DNA damage repair. Somatic mutation analysis in CHEK2 variant carriers showed mutations in TP53, APC, and FBXW7. Loss of heterozygosity was found in carcinoma of CHEK2 variant carrier, and IHC showed loss of Chk2 expression in cancer tissue. We identified a second variant in CHEK2 in 126 sporadic CRCs. A KO cellular model for CHEK2 (CHEK2KO) was generated by CRISPR/Cas9. Functional experiments demonstrated that CHEK2KO cells showed defective cell cycle arrest and apoptosis, as well as reduced p53 phosphorylation, upon DNA damage. We associated germline mutations in genes that regulate the DNA repair pathway with the development of CRC. We identified CHEK2 as a regulator of DNA damage response and perhaps as a gene involved in CRC germline predisposition. These findings link CRC predisposition to the DNA repair pathway, supporting the connection between genome integrity and cancer risk.
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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.