Activating mutation in MET oncogene in familial colorectal cancer

Neklason, Deborah W.; Done, Michelle W.; Sargent, Nykole R; Schwartz, Ann G.; Anton‐Culver, Hoda; Griffin, Constance A.; Ahnen, Dennis J.; Schildkraut, Joellen M.; Tomlinson, Gail E.; Strong, Louise C.; Miller, Alexander; Burt, Randall W.

doi:10.1186/1471-2407-11-424

Cited by 41 publications

(36 citation statements)

References 26 publications

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“…After the discovery of MET mutations in HRPC, studies in other solid tumors identified MET kinase domain mutations and some mutations outside the kinase domain in childhood hepatocellular carcinomas, breast cancer, colorectal cancer (CRC), head and neck squamous cell cancers (HNSCC), gastric carcinomas (GC), and cancers of unknown primary origin (CUP) (Figure 1) (13)(14)(15)(16)(17)(18)(19)(20)(21). For several years after the initial discovery, the small number of MET kinase activating mutations identified in other carcinomas suggested that mutations within the MET kinase domain were rare events in cancer.…”

Section: Met Kinase Domain Mutations In Hereditary Papillary Renal Camentioning

confidence: 99%

MET in human cancer: germline and somatic mutations

Tovar

Graveel

2017

Ann. Transl. Med.

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Since the initial discovery of missense MET mutations in hereditary papillary renal carcinoma (HPRC), activating MET mutations have been identified in a diverse range of human cancers. MET mutations have been identified in several functional domains including the kinase, juxtamembrane, and Sema domains. Studies of these mutations have been invaluable for our understanding of the tumor initiating activity of MET, receptor tyrosine kinase (RTK) recycling and regulation, and mechanisms of resistance to kinase inhibition. These studies also demonstrate that mutationally activated MET plays a significant role in a wide range of cancers and RTKs can promote tumor progression through diverse mechanisms. This review will cover the various MET mutations that have been identified, their mechanism of action, and the significant role that mutationally-activated MET plays in tumor initiation, progression, and therapeutic resistance.

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Section: Met Kinase Domain Mutations In Hereditary Papillary Renal Camentioning

confidence: 99%

MET in human cancer: germline and somatic mutations

Tovar

Graveel

2017

Ann. Transl. Med.

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“…MET mutations have been described in a variety of tumor types, spanning all domains of the MET gene. Both somatic and germline variants of MET have been reported in various human cancers, such as gastrointestinal malignancies [25,26]. In hereditary papillary renal cell cancer, TK domain gain-of-function mutations are demonstrated as oncogenic drivers.…”

Section: Discussionmentioning

confidence: 99%

Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer patients

et al. 2014

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MET has been suggested to have an intimate relationship with small cell lung cancer (SCLC) and might be a promising therapeutic target. To date, relatively limited reports have been explored on MET mutational status in SCLC patients. To investigate the relationship between MET mutations and SCLC, 68 Chinese patients surgically treated for SCLC were enrolled. MET mutational analyses were performed in tumors, adjacent normal tissues as well as in lymph nodes with no metastasis nonadherent to tumor tissues using Sanger sequencing after PCR. The same mutation types were found in tumors, adjacent normal tissues as well as lymph nodes, including the only missense mutation N375S encoding semaphorin domain in exon 2 in 4 patients (5.9%), one single-nucleotide polymorphism (SNP) rs35775721: C>T also encoding semaphorin domain as heterozygous in 10 cases (14.7%) and another SNP rs41736: C>T encoding tyrosine kinase domain in exon 20 existing in 49 cases (72.1%). In survival analysis, the wild genotype CC-carriers of rs41736 conferred a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to CT + TT-carriers (HR 0.455, 95% CI 0.229-0.904; HR 0.226, 95% CI 0.099-0.515, for PFS and OS, respectively) in limited-stage SCLC patients. We also found that the lymph node status was significantly associated with OS, and the shorter OS was present in positive group (HR 2.187, 95% CI 1.170-4.088). In this study, rs41736 polymorphism of MET was first found to be associated with prognosis of limited-stage SCLC patients and could be considered as a prognostic marker for limited-stage SCLC.

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“…Since then, various Met mutations that lead to a constitutively activation of the receptor were described and many of them are located in the juxtamembrane [196] and in the kinase [195] domain. In recent studies it was shown that Met point mutations in non hereditary CRC are rare events [197,198]. The high Met expression observed in colorectal tumors and liver metastases is more frequently induced by genomic amplifications of the Met gene [199].…”

Section: The Hgf/met Pathway In Cancer and Crc Metastasismentioning

confidence: 99%

Anti-metastatic Treatment in Colorectal Cancer: Targeting Signaling Pathways

Lemos¹,

Sack²,

Schmid³

et al. 2013

Current Pharmaceutical Design

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Colorectal cancer is one of the most common cancers worldwide and one of the leading causes of cancer-related death in the Western world. Tumor progression towards metastasis affects a large number of patients with colorectal cancer and seriously affects their clinical outcome. Therefore, considerable effort has been made towards the development of therapeutic strategies that can decrease or prevent colorectal cancer metastasis. Standard treatment of metastatic colorectal cancer with chemotherapy has been improved in the last 10 years by the addition of new targeted agents. The currently used antibodies bevacizumab, cetuximab and panitumumab target the VEGF and EGFR signaling pathways, which are crucial for tumor progression and metastasis. These antibodies have shown relevant efficacy in both first- and second-line treatment of metastatic colorectal cancer. Additionally, other signaling pathways, including the Wnt and HGF/Met pathways, have a well-established role in colorectal cancer progression and metastasis and constitute, therefore, promising targets for new therapeutic approaches. Several new drugs targeting these pathways, including different antibodies and small-molecule tyrosine kinase inhibitors, are currently being developed and tested in clinical trials. In this review, we summarize the new developments in this field, focusing on the inhibitors that show more promising results for use in colorectal cancer patients.

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Activating mutation in MET oncogene in familial colorectal cancer

Cited by 41 publications

References 26 publications

MET in human cancer: germline and somatic mutations

MET in human cancer: germline and somatic mutations

Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer patients

Anti-metastatic Treatment in Colorectal Cancer: Targeting Signaling Pathways

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