ArticleBMC cancer2011
Activating mutation in MET oncogene in familial colorectal cancer.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- The developmental factor TBX3 engages with the Wnt/β-catenin transcriptional complex in colorectal cancer to regulate metastasis genes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications.Cancers · 2025Review
- MET Exon 14 Skipping and Novel Actionable Variants: Diagnostic and Therapeutic Implications in Latin American Non-Small-Cell Lung Cancer Patients.International journal of molecular sciences · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- EGFR and PI3K Signalling Pathways as Promising Targets on Circulating Tumour Cells from Patients with Metastatic Gastric Adenocarcinoma.International journal of molecular sciences · 2024Article
- An Observatory for theCancers · 2023Review
- Canadian Consensus Recommendations on the Management ofCurrent oncology (Toronto, Ont.) · 2021Article
- The role of MET in chemotherapy resistance.Oncogene · 2021Review
- Co-stimulatory and co-inhibitory immune markers in solid tumors withFuture science OA · 2020Article
- MET and RON receptor tyrosine kinases in colorectal adenocarcinoma: molecular features as drug targets and antibody-drug conjugates for therapy.Journal of experimental & clinical cancer research : CR · 2020Review
- Article
- Therapeutic implications of germline genetic findings in cancer.Nature reviews. Clinical oncology · 2019Review
- Evaluation of MET T1010I and MET rs40239 single-nucleotide polymorphisms in triple-negative breast cancer: a case-control study.OncoTargets and therapy · 2019Article
- Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations.PLoS genetics · 2018Article
- Expanding the spectrum of germline variants in cancer.Human genetics · 2017Article
- MET in human cancer: germline and somatic mutations.Annals of translational medicine · 2017Review
- Review
- Epigenetic Biomarkers in Colorectal Cancer.Molecular diagnosis & therapy · 2017Review
- Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing.Familial cancer · 2017Article
- Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet?Journal of Cancer · 2016Review
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Authors and funding
13 authors at 11 institutions in 1 country.
Funding
Abstract
backgroundIn developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility.
methodsMET exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies). Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C >T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors.
resultsHere we report a germline non-synonymous change in the MET proto-oncogene at amino acid position T992I (also reported as MET p.T1010I) in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in <1% in the general population. The threonine at amino acid position 992 lies in the tyrosine kinase domain of MET and a change to isoleucine at this position has been shown to promote metastatic behavior in cell-based models. The average age of CRC diagnosis in patients in this study is 63 years in mutation carriers, which is 8 years earlier than the general population average for CRC.
conclusionsAlthough the MET p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will be an important extension of this work to define the clinical significance.
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