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

Hironori Ninomiya1, Motohiro Kato, Masashi Sanada

  • 1Division of Pathology, The Cancer Institute, Ariake 3-8-31, Koutou-ku, Tokyo 135-8550, Japan.

BMC Cancer
|January 8, 2013
PubMed
Abstract

Insights

Lung adenocarcinomas with EML4-ALK fusion show fewer genomic alterations in oncogenes and tumor suppressor genes. This suggests ALK fusion strongly drives cancer, even with similar overall aberration rates.

Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • A subset of lung adenocarcinomas features an EML4-ALK fusion gene, driving oncogenic activity and serving as a therapeutic target.
  • EML4-ALK fusion is associated with specific histology and is more prevalent in never/light smokers and younger patients.

Purpose of the Study:

  • To investigate the etiological and carcinogenic mechanisms of EML4-ALK fusion-positive lung adenocarcinomas.
  • To compare the genomic profiles of tumors with and without EML4-ALK fusion.

Main Methods:

  • Utilized single nucleotide polymorphism (SNP) arrays for precise global genomic profiling.
  • Analyzed allelotypes of 35 ALK fusion-positive and 95 ALK fusion-negative tumors.
  • Employed specially designed software for detailed genomic analysis.

Main Results:

  • Tumors with ALK fusion exhibited similar overall chromosomal alteration frequencies (gains + losses) compared to ALK-negative tumors.
  • Significantly fewer gains were observed in oncogene regions (e.g., MYCL1, EGFR, MYC, ERBB2) in ALK fusion-positive tumors.
  • Tumors with ALK fusion also showed significantly fewer alterations in tumor suppressor gene regions (e.g., CDKN2A, RB1).

Conclusions:

  • Global genomic profiling reveals that ALK fusion-positive lung adenocarcinomas have fewer alterations in key oncogenes and tumor suppressor genes.
  • The findings suggest a potent oncogenic role for ALK activation via gene fusion in lung adenocarcinoma development.

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