Identification and characterization of RET fusions in advanced colorectal cancer

Autor: Christopher R. Garrett, Tara Elisabeth Seery, Jeffrey S. Ross, Samuel J. Klempner, Eric M. Sanford, Vincent A. Miller, Anne-France Le Rolle, Siraj M. Ali, Philip J. Stephens, Sohail Balasubramanian, Vi K. Chiu
Rok vydání: 2015
Předmět:
Male
Neuroblastoma RAS viral oncogene homolog
congenital
hereditary
and neonatal diseases and abnormalities
endocrine system
Time Factors
endocrine system diseases
Cell Survival
Colorectal cancer
Nuclear Receptor Coactivators
colorectal cancer
Antineoplastic Agents
medicine.disease_cause
Bioinformatics
Fusion gene
Databases
Genetic
Biomarkers
Tumor
Humans
Medicine
Genetic Predisposition to Disease
Prospective Studies
Protein Kinase Inhibitors
neoplasms
RET fusion kinase
RET kinase inhibitor
Dose-Response Relationship
Drug
comprehensive genomic profiling
business.industry
Kinase
Gene Expression Profiling
Proto-Oncogene Proteins c-ret
High-Throughput Nucleotide Sequencing
Middle Aged
medicine.disease
Phenotype
digestive system diseases
Cytoskeletal Proteins
Treatment Outcome
Oncology
Cancer cell
Cancer research
Female
KRAS
Gene Fusion
Colorectal Neoplasms
business
Tyrosine kinase
Research Paper
Zdroj: Oncotarget
Le Rolle, AF; Klempner, SJ; Garrett, CR; Seery, T; Sanford, EM; Balasubramanian, S; et al.(2015). Identification and characterization of RET fusions in advanced colorectal cancer. Oncotarget, 6(30), 28929-28937. doi: 10.18632/oncotarget.4325. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/2749k799
ISSN: 1949-2553
DOI: 10.18632/oncotarget.4325
Popis: 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.
Databáze: OpenAIRE
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