MET in human cancer: germline and somatic mutations

Tovar, Elizabeth A.; Graveel, Carrie R.

doi:10.21037/atm.2017.03.64

Cited by 69 publications

(54 citation statements)

References 45 publications

(43 reference statements)

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“…Although our findings seem inferior to what recently reported by Drillon and colleagues in PROFILE 1001, in which PFS exceed 7 months and OS is approximately 20 months, differences in patients selection limit comparison between the two studies (30). Exon 14 mutations include a wide range of abnormalities, such as insertion, deletion, or point mutation that generally lead the loss or attenuation of ubiquitinmediated receptor degradation, for instance, by disrupting the splice acceptor site of intron 13 or affecting the splice donor site of intron 14 (8,27,32). How different mutations could affect sensitivity to MET inhibitors, especially crizotinib, remains an unanswered question.…”

Section: Discussionmentioning

confidence: 99%

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Landi

Chiari

Tiseo

et al. 2019

Clinical Cancer Research

153

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Purpose: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations.Patients and Methods: Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 >2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts.Results: From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2-30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0-5.8), and overall survival was 5.4 months (95% CI, 4.2-6.5). No difference in any clinical endpoint was observed between MET-amplified and exon 14-mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts.Conclusions: Crizotinib induces response in a fraction of MET-deregulated NSCLC. Additional studies and innovative therapies are urgently needed.

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Section: Discussionmentioning

confidence: 99%

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Landi

Chiari

Tiseo

et al. 2019

Clinical Cancer Research

153

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“…A well‐known mutation in MET gene can be seen in hepatocellular carcinoma of childhood. This cancer is caused because of a somatic mutation in the kinase domain of MET . Despite the presence of activating mutations, some MET mutations are considered to be inhibitors of downregulation.…”

Section: Role Of C‐met/hgf Signaling Pathway In Carcinogenesismentioning

confidence: 99%

The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer

et al. 2019

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Colorectal cancer (CRC) is the third most common cancer and a common cause of cancer‐related mortality globally. In spite of the improvements in the early diagnosis of CRC, approximately one‐third of patients develop metastasis and then have a very poor survival rate. The mesenchymal–epithelial transition factor (c‐MET) is a tyrosine kinase cell surface receptor activated by hepatocyte growth factor (HGF). Activation of c‐MET/HGF signaling pathway regulates a variety of biological processes including cell motility, cell proliferation, angiogenesis, the epithelial‐to‐mesenchymal transition, and the development and progression of cancer cells. Recent studies have suggested that the c‐MET/HGF signaling pathway is involved in the carcinogenesis of CRC. In this review, we summarize the main findings of recent studies investigating the role of c‐MET/HGF signaling pathway in CRC and the potential of the c‐MET/HGF signaling pathways in the diagnosis and treatment of CRC. © 2019 IUBMB Life, 2019

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“…The same strategy is possible in type I HPRC because of the germline MET mutations. However, type I HPRCs are less malignant than type II tumors, enabling physicians to choose the proper surgical strategy (3,14).…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, hereditary papillary renal carcinoma (HPRC, or PRCC1, OMIM 605074) is an autosomal dominant disease characterized by the development of multiple papillary type I renal cell carcinomas. This hereditary RCC form is caused by activating mutations in the MET proto-oncogene on chromosome 7q31 (3,4). MET encodes for a receptor of the hepatocyte growth factor (HGF), which affects many cell types despite its name.…”

Section: Introductionmentioning

confidence: 99%

Case of Hereditary Papillary Renal Cell Carcinoma Type I in a Patient With a Germline MET Mutation in Russia

et al. 2020

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Hereditary papillary renal carcinoma (HPRC) is a rare autosomal dominant disease characterized by the development of multiple papillary type I renal cell carcinomas. This hereditary kidney cancer form is caused by activating mutations in MET. Descriptions of patients with HPRC are scarce in the world literature, and no cases have been described in open sources in Russia. Here, we describe a 28-year-old female Russian patient with 7 and 10 primary papillary renal cell carcinomas in the left and right kidneys, respectively. The patient did not have a family history of any of the known hereditary cancer syndromes. A comprehensive medical examination was performed in 2016 including computed tomography and pathomorphological analysis. The observed tumors were resected in a two-step surgical treatment. In February 2019, no sign of disease progression was detected in follow-up medical examination. Molecular genetic analysis revealed the germline heterozygous missense variant in MET: c.3328G>A (p.V1110I; CM990852). We have discussed the biological effects of the detected mutation and the utility of DNA diagnostics for treating patients with HPRC.

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MET in human cancer: germline and somatic mutations

Cited by 69 publications

References 45 publications

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

The potential therapeutic and prognostic impacts of the c‐MET/HGF signaling pathway in colorectal cancer

Case of Hereditary Papillary Renal Cell Carcinoma Type I in a Patient With a Germline MET Mutation in Russia

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