ArticleOncotarget2017
BRCA2, EGFR, and NTRK mutations in mismatch repair-deficient colorectal cancers with MSH2 or MLH1 mutations.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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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
16 citing papers in PubMed, 39 citations in OpenAlex.
- Detection of oncogenic fusions in colorectal cancer using a partner-agnostic next-generation sequencing approach.BMC cancer · 2025Article
- Coexisting germline variants ofInternational cancer conference journal · 2025Article
- Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Recommended testing algorithms for NTRK gene fusions in pediatric and selected adult cancers: Consensus of a Singapore Task Force.Asia-Pacific journal of clinical oncology · 2022Article
- NTRK gene fusions in solid tumors: agnostic relevance, prevalence and diagnostic strategies.Pathologica · 2022Review
- Characteristic mutations induced in the small intestine of Msh2-knockout gpt delta mice.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Article
- ARID1A genomic alterations driving microsatellite instability through somatic MLH1 methylation with response to immunotherapy in metastatic lung adenocarcinoma: a case report.Journal of medical case reports · 2021Article
- An Accurate and Comprehensive Clinical Sequencing Assay for Cancer Targeted and Immunotherapies.The oncologist · 2019Article
- Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2019Review
- Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Selected Office Based Anticancer Treatment Strategies.Journal of oncology · 2019Review
- Recent progress in Lynch syndrome and other familial colorectal cancer syndromes.CA: a cancer journal for clinicians · 2018Review
- Preclinical rationale for combination of crizotinib with mitomycin C for the treatment of advanced colorectal cancer.Cancer biology & therapy · 2017Article
- Mismatch repair deficient metastatic colon cancer and urothelial cancer: A case report of sequential immune checkpoint therapy.Cancer biology & therapy · 2017Article
- MMR-deficiency and BRCA2/EGFR/NTRK mutations.Aging · 2017Article
- New perspectives for colorectal cancer.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Deficient mismatch repair (MMR) and microsatellite instability (MSI) contribute to ~15% of colorectal cancer (CRCs). We hypothesized MSI leads to mutations in DNA repair proteins including BRCA2 and cancer drivers including EGFR. We analyzed mutations among a discovery cohort of 26 MSI-High (MSI-H) and 558 non-MSI-H CRCs profiled at Caris Life Sciences. Caris-profiled MSI-H CRCs had high mutation rates (50% vs 14% in non-MSI-H, P < 0.0001) in BRCA2. Of 1104 profiled CRCs from a second cohort (COSMIC), MSH2/MLH1-mutant CRCs showed higher mutation rates in BRCA2 compared to non-MSH2/MLH1-mutant tumors (38% vs 6%, P < 0.0000001). BRCA2 mutations in MSH2/MLH1-mutant CRCs included 75 unique mutations not known to occur in breast or pancreatic cancer per COSMIC v73. Only 5 deleterious BRCA2 mutations in CRC were previously reported in the BIC database as germ-line mutations in breast cancer. Some BRCA2 mutations were predicted to disrupt interactions with partner proteins DSS1 and RAD51. Some CRCs harbored multiple BRCA2 mutations. EGFR was mutated in 45.5% of MSH2/MLH1-mutant and 6.5% of non-MSH2/MLH1-mutant tumors (P < 0.0000001). Approximately 15% of EGFR mutations found may be actionable through TKI therapy, including N700D, G719D, T725M, T790M, and E884K. NTRK gene mutations were identified in MSH2/MLH1-mutant CRC including NTRK1 I699V, NTRK2 P716S, and NTRK3 R745L. Our findings have clinical relevance regarding therapeutic targeting of BRCA2 vulnerabilities, EGFR mutations or other identified oncogenic drivers such as NTRK in MSH2/MLH1-mutant CRCs or other tumors with mismatch repair deficiency.
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