Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes
1 Division of Pathology, The Cancer Institute, Ariake 3-8-31, Koutou-ku, 135-8550, Tokyo, Japan
2 Pathology Project for Molecular Targets, The Cancer Institute, Ariake 3-8-31, Koutou-ku, 135-8550, Tokyo, Japan
3 Thoracic Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake 3-8-31, Koutou-ku, 135-8550, Tokyo, Japan
4 Cancer Genomics Project, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-8656, Tokyo, Japan
5 Department of Pediatrics, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-8656, Tokyo, Japan
6 Department of Medical Genomics, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-8656, Tokyo, Japan
7 Division of Functional Genomics, Jichi Medical University, 329-0498, Tochigi, Japan
Citation and License
BMC Cancer 2013, 13:8 doi:10.1186/1471-2407-13-8Published: 5 January 2013
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.
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.
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.
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.