Abstract 3853: Unique pattern of copy number changes including chromothripsis in pulmonary adenocarcinoma with EML4-ALK fusion

Abstract

Abstract Background: A subset of lung adenocarcinomas harbors an ALK fusion gene resulting in dominant oncogenic activity. Gene inversion may play a main role in forming the fusion, not producing copy number changes. But its detailed mechanism leading to gene fusion remains unsolved. MATERIAL AND METHODS: To elucidate the underlying mechanisms resulting in gene fusion, two cancer cell lines positive for EML4-ALK fusion and surgically resected frozen specimens (33 ALK fusion-positive and 95 ALK fusion-negative adenocarcinomas) were analyzed using Affymetrix CytoScan HD Array with Chromosome Analysis Suite (ChAS) software for cell lines (JFCR-LC649 and JFCR-LC654) and Affymetrix GeneChip Mapping 250K arrays for surgical specimens. RESULTS: One (JFCR-LC649) of the two cell lines with gene fusion showed an extremely frequent change of copy number, or “copy number oscillation”, which we thought was chromothripsis. In surgical materials, 30% (10/33) of adenocarcinomas with ALK fusion harbored frequent copy number changes at various degrees, but not like the “oscillation” pattern. None of the 95 resected cases without ALK fusion showed similar genomic aberrations. These results from the JFCR-LC649 line and the 10 surgical cases indicated that genomic changes resulting in copy number alterations (including chromothripsis) as well as a simple inversion may cause gene fusion. CONCLUSION: As well as genome inversion, copy number alterations such as chromothripsis contribute to gene rearrangements resulting in the EML4-ALK fusion. Citation Format: Hironori Ninomiya, Motohiro Kato, Seishi Ogawa, Noriko Motoi, Kengo Takeuchi, Tatsushi Kodama, Hiroshi Sakamoto, Nobuya Ishii, Mutsunori Fujiwara, Yuichi Ishikawa. Unique pattern of copy number changes including chromothripsis in pulmonary adenocarcinoma with EML4-ALK fusion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3853. doi:10.1158/1538-7445.AM2015-3853