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

• Published in: Nature medicine Vol. 18; no. 3; pp. 382 - 384
• Main Authors: Lipson, Doron, 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2012; Nature Publishing Group
• Subjects: 631/208/199; 692/699/67/1504/1885; 692/699/67/1612/1350; 692/700/139; Adenocarcinoma; Anaplastic Lymphoma Kinase; Animals; Biomedical and Life Sciences; Biomedicine; Biopsy; brief-communication; Cancer Research; Carcinoma, Non-Small-Cell Lung - genetics; Care and treatment; Cell Transformation, Neoplastic - drug effects; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Genomics; High-Throughput Nucleotide Sequencing; Humans; Infectious Diseases; Inhibitors; Introns; Janus kinase 2; Kinases; Kinesins - antagonists & inhibitors; Kinesins - genetics; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Metabolic Diseases; Mice; Molecular Medicine; Mutation; Neurosciences; Next-generation sequencing; NIH 3T3 Cells; Non-small cell lung carcinoma; Oncogene Proteins, Fusion - genetics; Paraffin; Paraffins; Physiological aspects; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-ret - antagonists & inhibitors; Proto-Oncogene Proteins c-ret - genetics; Receptor Protein-Tyrosine Kinases - genetics; Ret protein; Risk factors; Tumors; United States
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.2673

Using high-coverage targeted next-generation sequencing, this report provides a catalog of genetic alterations in colorectal and lung cancers, identifying previously unknown alterations, such as JAK2 mutations and KIF5B-RET fusions, that may represent druggable targets. 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.