Oncotarget

Priority Research Papers:

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 and Ana M. Gonzalez-Angulo

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Oncotarget. 2015; 6:2604-2614. https://doi.org/10.18632/oncotarget.3094

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Abstract

Shuying Liu1,2, Funda Meric-Bernstam3, Napa Parinyanitikul1, Bailiang Wang1, Agda K. Eterovic2, Xiaofeng Zheng4, Mihai Gagea5, Mariana Chavez-MacGregor1, Naoto T. Ueno1,6, Xiudong Lei7, Wanding Zhou4, Lakshmy Nair1, Debu Tripathy1, Powel H. Brown8, Gabriel N. Hortobagyi1, Ken Chen4, John Mendelsohn9, Gordon B. Mills2 and Ana M. Gonzalez-Angulo1,2

1 Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

3 Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

4 Department of Bioinformatics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

5 Department of Veterinary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

6 Section of Breast Cancer Translational Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

7 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

8 Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

9 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence:

Shuying Liu, email:

Keywords: MET mutations, Breast Cancer, Malignant transformation

Received: September 09, 2014 Accepted: December 24, 2014 Published: December 31, 2014

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 in-vitro 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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