Functional consequence of the MET-T1010I polymorphism in breast cancer

Shuying Liu; Funda Meric-Bernstam; Napa Parinyanitikul; Bailiang Wang; Agda K. Eterovic; Xiaofeng Zheng; Mihai Gagea; Mariana Chavez-MacGregor; Naoto T. Ueno; Xiudong Lei; Wanding Zhou; Lakshmy Nair; Debu Tripathy; Powel H. Brown; Gabriel N. Hortobagyi; Ken Chen; John Mendelsohn; Gordon B. Mills; Ana M. Gonzalez-Angulo

doi:10.18632/oncotarget.3094

Functional consequence of the MET-T1010I polymorphism in breast cancer

Shuying Liu, Funda Meric-Bernstam, Napa Parinyanitikul, Bailiang Wang, Agda K. Eterovic, Xiaofeng Zheng, Mihai Gagea, Mariana Chavez-MacGregor, Naoto T. Ueno, Xiudong Lei, Wanding Zhou, Lakshmy Nair, Debu Tripathy, Powel H. Brown, Gabriel N. Hortobagyi, Ken Chen, John Mendelsohn, Gordon B. Mills, Ana M. Gonzalez-Angulo

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion invitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials.

Original language	English (US)
Pages (from-to)	2604-2614
Number of pages	11
Journal	Oncotarget
Volume	6
Issue number	5
DOIs	https://doi.org/10.18632/oncotarget.3094
State	Published - 2015
Externally published	Yes

Keywords

Breast cancer
MET mutations
Malignant transformation

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.3094

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Liu, S., Meric-Bernstam, F., Parinyanitikul, N., Wang, B., Eterovic, A. K., Zheng, X., Gagea, M., Chavez-MacGregor, M., Ueno, N. T., Lei, X., Zhou, W., Nair, L., Tripathy, D., Brown, P. H., Hortobagyi, G. N., Chen, K., Mendelsohn, J., Mills, G. B., & Gonzalez-Angulo, A. M. (2015). Functional consequence of the MET-T1010I polymorphism in breast cancer. Oncotarget, 6(5), 2604-2614. https://doi.org/10.18632/oncotarget.3094

Liu, S, Meric-Bernstam, F, Parinyanitikul, N, Wang, B, Eterovic, AK, Zheng, X, Gagea, M, Chavez-MacGregor, M, Ueno, NT, Lei, X, Zhou, W, Nair, L, Tripathy, D, Brown, PH, Hortobagyi, GN, Chen, K, Mendelsohn, J, Mills, GB & Gonzalez-Angulo, AM 2015, 'Functional consequence of the MET-T1010I polymorphism in breast cancer', Oncotarget, vol. 6, no. 5, pp. 2604-2614. https://doi.org/10.18632/oncotarget.3094

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abstract = "Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion invitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials.",

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AU - Nair, Lakshmy

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AU - Brown, Powel H.

AU - Hortobagyi, Gabriel N.

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AU - Mills, Gordon B.

AU - Gonzalez-Angulo, Ana M.

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Functional consequence of the MET-T1010I polymorphism in breast cancer

Abstract

Keywords

ASJC Scopus subject areas

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