Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer

Dan R. Robinson, Shanker Kalyana-Sundaram, Yi Mi Wu, Sunita Shankar, Xuhong Cao, Bushra Ateeq, Irfan A. Asangani, Matthew Iyer, Christopher Maher, Catherine S. Grasso, Robert J. Lonigro, Michael Quist, Javed Siddiqui, Rohit Mehra, Xiaojun Jing, Thomas J. Giordano, Michael S. Sabel, Celina G. Kleer, Nallasivam Palanisamy, Rachael NatrajanMaryou B. Lambros, Jorge S. Reis-Filho, Chandan Kumar-Sinha, Arul M. Chinnaiyan

Research output: Contribution to journalArticle

210 Scopus citations

Abstract

Breast cancer is a heterogeneous disease that has a wide range of molecular aberrations and clinical outcomes. Here we used paired-end transcriptome sequencing to explore the landscape of gene fusions in a panel of breast cancer cell lines and tissues. We observed that individual breast cancers have a variety of expressed gene fusions. We identified two classes of recurrent gene rearrangements involving genes encoding microtubule-associated serine-threonine kinase (MAST) and members of the Notch family. Both MAST and Notch-family gene fusions have substantial phenotypic effects in breast epithelial cells. Breast cancer cell lines harboring Notch gene rearrangements are uniquely sensitive to inhibition of Notch signaling, and overexpression of MAST1 or MAST2 gene fusions has a proliferative effect both in vitro and in vivo. These findings show that recurrent gene rearrangements have key roles in subsets of carcinomas and suggest that transcriptome sequencing could identify individuals with rare, targetable gene fusions.

Original languageEnglish
Pages (from-to)1646-1651
Number of pages6
JournalNature medicine
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2011

Fingerprint Dive into the research topics of 'Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Robinson, D. R., Kalyana-Sundaram, S., Wu, Y. M., Shankar, S., Cao, X., Ateeq, B., Asangani, I. A., Iyer, M., Maher, C., Grasso, C. S., Lonigro, R. J., Quist, M., Siddiqui, J., Mehra, R., Jing, X., Giordano, T. J., Sabel, M. S., Kleer, C. G., Palanisamy, N., ... Chinnaiyan, A. M. (2011). Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer. Nature medicine, 17(12), 1646-1651. https://doi.org/10.1038/nm.2580