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Oncotarget. 2015 Oct 6;6(30):28929-37. doi: 10.18632/oncotarget.4325.

Identification and characterization of RET fusions in advanced colorectal cancer.

Author information

1
Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, CA, USA.
2
Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA, USA.
3
The Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
4
Foundation Medicine Inc., Cambridge, MA, USA.
5
Albany Medical College, Albany, NY, USA.

Abstract

There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC.

KEYWORDS:

RET fusion kinase; RET kinase inhibitor; colorectal cancer; comprehensive genomic profiling

PMID:
26078337
PMCID:
PMC4745701
DOI:
10.18632/oncotarget.4325
[Indexed for MEDLINE]
Free PMC Article

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