ArticleJCI insight2020
Germline biallelic Mcm8 variants are associated with early-onset Lynch-like syndrome.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Unexplained mismatch repair deficiency: Case closed.HGG advances · 2023Pooled it
- Closing the Diagnostic Gap in Early-Onset Colorectal Cancer: Red-Flag Symptoms, Screening, and Inherited Risk.Cancers · 2026Review
- Lynch Syndrome: An Update of Underlying Molecular Mechanisms, Phenotypes and Methods to Classify Variants of Uncertain Significance.Biomedicines · 2026Review
- MCM8 promotes colorectal cancer progression by competitively inhibiting HRD1-mediated CDC42 ubiquitination and degradation.Journal of translational medicine · 2026Article
- Review
- APhenomics (Cham, Switzerland) · 2025Article
- Incidence and molecular characteristics of deficient mismatch repair conditions across nine different tumors and identification of germline variants involved in Lynch-like syndrome.International journal of clinical oncology · 2024Article
- Mechanism of DNA unwinding by MCM8-9 in complex with HROB.Nature communications · 2024Article
- MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease.Nature cardiovascular research · 2023Article
- Mechanism of DNA unwinding by hexameric MCM8-9 in complex with HROB.Research square · 2023Article
- Review
- The Role ofJournal of clinical medicine · 2023Article
- Lynch Syndrome Identification in Saudi Cohort of Endometrial Cancer Patients Screened by Universal Approach.International journal of molecular sciences · 2022Article
- Whole-Exome Sequencing Identifies Pathogenic Germline Variants in Patients with Lynch-Like Syndrome.Cancers · 2022Article
- Review
- Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis.Cancers · 2022Review
- MCM9 is associated with germline predisposition to early-onset cancer-clinical evidence.NPJ genomic medicine · 2021Article
- Germline mutations in a DNA repair pathway are associated with familial colorectal cancer.JCI insight · 2021Article
- Genetic Factors of Non-Obstructive Azoospermia: Consequences on Patients' and Offspring Health.Journal of clinical medicine · 2021Review
- Review
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lynch syndrome is the most common cause of hereditary colorectal cancer (CRC), and it is characterized by DNA mismatch repair (MMR) deficiency. The term Lynch-like syndrome (LLS) is used for patients with MMR-deficient tumors and neither germline mutation in MLH1, MSH2, MSH6, PMS2, or EPCAM nor MLH1 somatic methylation. Biallelic somatic inactivation or cryptic germline MMR variants undetected during genetic testing have been proposed to be involved. Sixteen patients with early-onset LLS CRC were selected for germline and tumor whole-exome sequencing. Two potentially pathogenic germline MCM8 variants were detected in a male patient with LLS with fertility problems. A knockout cellular model for MCM8 was generated by CRISPR/Cas9 and detected genetic variants were produced by mutagenesis. DNA damage, microsatellite instability, and mutational signatures were monitored. DNA damage was evident for MCM8KO cells and the analyzed genetic variants. Microsatellite instability and mutational signatures in MCM8KO cells were compatible with the involvement of MCM8 in MMR. Replication in an independent familial cancer cohort detected additional carriers. Unexplained MMR-deficient CRC cases, even showing somatic biallelic MMR inactivation, may be caused by underlying germline defects in genes different than MMR genes. We suggest MCM8 as a gene involved in CRC germline predisposition with a recessive pattern of inheritance.
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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.