Artículo de revista
Arsenic-related DNA copy-number alterations in lung squamous cell carcinomas
Fecha
2010Registro en:
British Journal of Cancer (2010) 103, 1277 – 1283
15321827
00070920
10.1038/sj.bjc.6605879
Autor
Martínez, V. D.
Buys, T. P. H.
Adonis, M.
Benítez, H.
Gallegos, I.
Lam, S.
Lam, W. L.
Gil, L.
Institución
Resumen
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.