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Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies

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.

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Figure 1: DNA alterations identified in 40 CRC FFPE specimens.
Figure 2: DNA alterations identified in 24 NSCLC FFPE specimens.

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Acknowledgements

We would like to thank M. Hawryluk for his help in preparing this manuscript. This work is supported by the Dana Farber/Harvard Cancer Center Lung Cancer SPORE P50 CA090578 (P.A.J.), the Cammarata Family Foundation Research Fund (M.C. and P.A.J.), the Nirenberg Fellowship at the Dana-Farber Cancer Institute (M.C. and P.A.J.) and the Japan Society for the Promotion of Science (JSPS), grant references 23659674, 21390394 and 21591820 (H.S.).

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Authors

Contributions

D.L. and R.Y. designed experiments and algorithms, and performed analyses. J.W. and G.M.F. performed data analyses. A.P. and G.O. performed RNA preparations and prepared the cDNA libraries and sequencing. M.J. designed the experiments and performed analyses. J.A.C. and K.C.M. performed laboratory and project management. S.R.D. and T.B. performed tissue pathology preparations and extractions. J.S.R. provided tissue specimens and the pathology review. S.B., K.W.B., A.D., L.G., F.J., E.W. and Z.Z. performed DNA library preparation and sequencing. P.J.S., M.T.C. and P.A.J. designed experiments, analyzed data and wrote the manuscript. T.P., H.N., L.-S.G., C.E.S., J.K., H.S., H.R.K. and S.P. provided subject specimens. M.C. performed genotyping of subjects with lung cancer, conducted in vitro studies and analyzed data. D.E. performed in vitro studies.

Corresponding authors

Correspondence to Maureen T Cronin, Pasi A Jänne or Philip J Stephens.

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Competing interests

D.L., R.Y., G.O., A.P., M.J., J.A.C., S.B., T.B., K.W.B., A.D., S.R.D., G.M.F., L.G., F.J., K.C.M., E.W., J.W., Z.Z., M.T.C. and P.J.S. are employees of Foundation Medicine, Inc. J.S.R. is a consultant to Foundation Medicine, Inc.

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Lipson, D., Capelletti, M., Yelensky, R. et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 18, 382–384 (2012). https://doi.org/10.1038/nm.2673

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