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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes

Authors: Hironori Ninomiya, Motohiro Kato, Masashi Sanada, Kengo Takeuchi, Kentaro Inamura, Noriko Motoi, Hiroko Nagano, Kimie Nomura, Yukinori Sakao, Sakae Okumura, Hiroyuki Mano, Seishi Ogawa, Yuichi Ishikawa

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

A subset of lung adenocarcinomas harboring an EML4-ALK fusion gene resulting in dominant oncogenic activity has emerged as a target for specific therapy. EML4-ALK fusion confers a characteristic histology and is detected more frequently in never or light smokers and younger patients.

Methods

To gain insights into etiology and carcinogenic mechanisms we conducted analyses to compare allelotypes of 35 ALK fusion-positive and 95 -negative tumours using single nucleotide polymorphism (SNP) arrays and especially designed software which enabled precise global genomic profiling.

Results

Overall aberration numbers (gains + losses) of chromosomal alterations were 8.42 and 9.56 in tumours with and without ALK fusion, respectively, the difference not being statistically significant, although patterns of gain and loss were distinct. Interestingly, among selected genomic regions, oncogene-related examples such as 1p34.3(MYCL1), 7q11.2(EGFR), 7p21.1, 8q24.21(MYC), 16p13.3, 17q12(ERBB2) and 17q25.1 showed significantly less gain. Also, changes in tumour suppressor gene-related regions, such as 9p21.3 (CDKN2A) 9p23-24.1 (PTPRD), 13q14.2 (RB1), were significantly fewer in tumours with ALK fusion.

Conclusion

Global genomic comparison with SNP arrays showed tumours with ALK fusion to have fewer alterations in oncogenes and suppressor genes despite a similar overall aberration frequency, suggesting very strong oncogenic potency of ALK activation by gene fusion.
Appendix
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Metadata
Title
Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes
Authors
Hironori Ninomiya
Motohiro Kato
Masashi Sanada
Kengo Takeuchi
Kentaro Inamura
Noriko Motoi
Hiroko Nagano
Kimie Nomura
Yukinori Sakao
Sakae Okumura
Hiroyuki Mano
Seishi Ogawa
Yuichi Ishikawa
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-8

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