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PMID: 22327622 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature medicine ·Vol. 18 ·No. 3 ·2012-02-12 ·Pages 382-4

Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, Curran JA, Balasubramanian S, Bloom T, Brennan KW, Donahue A, Downing SR, Frampton GM, Garcia L, Juhn F, Mitchell KC, White E, White J, Zwirko Z, Peretz T, Nechushtan H, Soussan-Gutman L, Kim J, Sasaki H, Kim HR, Park SI, Ercan D, Sheehan CE, Ross JS, Cronin MT, Jänne PA, Stephens PJ

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.

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,genetics Lung Neoplasms/genetics,pathology Mice NIH 3T3 Cells Oncogene Proteins, Fusion/genetics Protein Kinase Inhibitors/pharmacology Proto-Oncogene Proteins c-ret/antagonists & inhibitors,genetics Receptor Protein-Tyrosine Kinases/genetics

Chemicals

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

Authors & Affiliations

32 authors, click to expand affiliations / ORCID

Lipson Doron

Foundation Medicine, Cambridge, Massachusetts, USA.

Capelletti Marzia

Yelensky Roman

Otto Geoff

Parker Alex

Jarosz Mirna

Curran John A

Balasubramanian Sohail

Bloom Troy

Brennan Kristina W

Donahue Amy

Downing Sean R

Frampton Garrett M

Garcia Lazaro

Juhn Frank

Mitchell Kathy C

White Emily

White Jared

Zwirko Zac

Peretz Tamar

Nechushtan Hovav

Soussan-Gutman Lior

Kim Jhingook

Sasaki Hidefumi

Kim Hyeong Ryul

Park Seung-il

Ercan Dalia

Sheehan Christine E

Ross Jeffrey S

Cronin Maureen T

Jänne Pasi A

Stephens Philip J

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Article Info

Journal

Nature medicine

Abbr.

Nat Med

ISSN

1546-170X

DOI

10.1038/nm.2673

Published

2012-02-12

Epub

2012-00-12

Pages

382-4

Language

English

Region

United States

NLM ID

9502015

PMCID

PMC3916180

Subset

Grants

NCI NIH HHS · P50 CA090578 · United States

NCI NIH HHS · R01 CA136851 · United States

Corrections

CommentIn

PMID: 22371133

CommentIn

PMID: 22395697

External Links

PubMed source DOI: 10.1038/nm.2673 PMC Full Text View journal details

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

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