Focus: Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability.

Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39) and NS (n = 30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms.

Source: Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability. Thu KL (kthu@bccrc.ca), Vucic EA, Chari R, Zhang W, Lockwood WW, English JC, Fu R, Wang P, Feng Z, Macaulay CE, Gazdar AF, Lam S, Lam WL. PLoS One. 2012;7(3):e33003.

Free paper available at: http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0033003&representation=PDF

Des données récentes suggèrent que les distinctions cliniques observés entre les tumeurs du poumon chez les fumeurs et les personnes n'ayant jamais fumé (« NS ») vont au-delà de mutations génétiques spécifiques, telles que celles touchant les gènes EGFR, EML4-ALK, et KRAS, dont certaines ont donné lieu à des thérapies ciblées. Les altérations moléculaires identifiées à ce jour ne peuvent cependant pas expliquer tous les disparités cliniques et biologiques observées dans les tumeurs du poumon des fumeurs et des « NS ». Nous avons effectué une étude comparative à l'échelle du génome visant à identifier de nouvelles aberrations génomiques qui diffèrent entre les fumeurs et les NS.  Nous avons constaté que les tumeurs du poumon provenant des NS avaient une plus grande proportion de leurs génomes modifiés que celles des fumeurs. En outre, les gains du nombre de copies sur les chromosomes 5q, 7P, et 16p sont survenus plus fréquemment chez les NS. Nous avons validé nos conclusions dans deux ensembles indépendants de données publiques.

Article (en anglais) librement accessible à l’adresse :

http://www.plosone.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0033003&representation=PDF