Abstract
Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non-small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8-3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anaplastic Lymphoma Kinase
-
Animals
-
Biopsy
-
Carcinoma, Non-Small-Cell Lung / genetics*
-
Cell Transformation, Neoplastic / drug effects
-
Colorectal Neoplasms / genetics*
-
Gene Expression Regulation, Neoplastic / drug effects
-
High-Throughput Nucleotide Sequencing
-
Humans
-
Kinesins / antagonists & inhibitors
-
Kinesins / genetics*
-
Lung Neoplasms / genetics*
-
Lung Neoplasms / pathology
-
Mice
-
NIH 3T3 Cells
-
Oncogene Proteins, Fusion / genetics*
-
Protein Kinase Inhibitors / pharmacology
-
Proto-Oncogene Proteins c-ret / antagonists & inhibitors
-
Proto-Oncogene Proteins c-ret / genetics*
-
Receptor Protein-Tyrosine Kinases / genetics*
Substances
-
KIF5B protein, human
-
Oncogene Proteins, Fusion
-
Protein Kinase Inhibitors
-
ALK protein, human
-
Alk protein, mouse
-
Anaplastic Lymphoma Kinase
-
Proto-Oncogene Proteins c-ret
-
RET protein, human
-
Receptor Protein-Tyrosine Kinases
-
Kinesins