Arsenic-related DNA copy-number alterations in lung squamous cell carcinomas

Abstract

BACKGROUND: Lung squamous cell carcinomas (SqCCs) occur at higher rates following arsenic exposure. Somatic DNA copy-number alterations (CNAs) are understood to be critical drivers in several tumour types. We have assembled a rare panel of lung tumours from a population with chronic arsenic exposure, including SqCC tumours from patients with no smoking history. METHODS: Fifty-two lung SqCCs were analysed by whole-genome tiling-set array comparative genomic hybridisation. Twenty-two were derived from arsenic-exposed patients from Northern Chile (10 never smokers and 12 smokers). Thirty additional cases were obtained for comparison from North American smokers without arsenic exposure. Twenty-two blood samples from healthy individuals from Northern Chile were examined to identify germline DNA copy-number variations (CNVs) that could be excluded from analysis. RESULTS: We identified multiple CNAs associated with arsenic exposure. These alterations were not attributable to either smoking status or CNVs. DNA losses at chromosomes 1q21.1, 7p22.3, 9q12, and 19q13.31 represented the most recurrent events. An arsenic-associated gain at 19q13.33 contains genes previously identified as oncogene candidates. CONCLUSIONS: Our results provide a comprehensive approach to molecular characteristics of the arsenic-exposed lung cancer genome and the non-smoking lung SqCC genome. The distinct and recurrent arsenic-related alterations suggest that this group of tumours may be considered as a separate disease subclass.