Diverse, biologically relevant, and targetable gene rearrangements in triple-negative breast cancer and other malignancies

Timothy M. Shaver, Brian D. Lehmann, J. Scott Beeler, Chung I. Li, Zhu Li, Hailing Jin, Thomas P. Stricker, Yu Shyr, Jennifer A. Pietenpol

研究成果: Article

20 引文 斯高帕斯(Scopus)

摘要

Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between noncoding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1. The over 1,000 genetic alterations we identified highlight the importance of considering noncoding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers.

原文English
頁(從 - 到)4850-4860
頁數11
期刊Cancer Research
76
發行號16
DOIs
出版狀態Published - 2016 八月 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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