Genomic and evolutionary classification of lung cancer in never smokers
Authors
Zhang, T.Joubert, P.
Ansari-Pour, N.
Zhao, W.
Hoang, P. H.
Lokanga, R.
Moye, A. L.
Rosenbaum, J.
Gonzalez-Perez, A.
Martínez-Jiménez, F.
Castro, A.
Muscarella, L. A.
Hofman, P.
Consonni, D.
Pesatori, A. C.
Kebede, M.
Li, M.
Gould Rothberg, B. E.
Peneva, I.
Schabath, M. B.
Poeta, M. L.
Costantini, M.
Hirsch, D.
Heselmeyer-Haddad, K.
Hutchinson, A.
Olanich, M.
Lawrence, S. M.
Lenz, P.
Duggan, M.
Bhawsar, P. M. S.
Sang, J.
Kim, J.
Mendoza, L.
Saini, N.
Klimczak, L. J.
Islam, S. M. A.
Otlu, B.
Khandekar, A.
Cole, N.
Stewart, D. R.
Choi, J.
Brown, K. M.
Caporaso, N. E.
Wilson, S. H.
Pommier, Y.
Lan, Q.
Rothman, N.
Almeida, J. S.
Carter, H.
Ried, T.
Kim, C. F.
Lopez-Bigas, N.
Garcia-Closas, M.
Shi, J.
Bossé, Y.
Zhu, B.
Gordenin, D. A.
Alexandrov, L. B.
Chanock, S. J.
Wedge, David C
Landi, M. T.
Affiliation
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USAIssue Date
2021
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Show full item recordAbstract
Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. The other subtypes are characterized by specific amplifications and EGFR mutations (mezzo-forte) and whole-genome doubling (forte). No strong tobacco smoking signatures were detected, even in cases with exposure to secondhand tobacco smoke. Genes within the receptor tyrosine kinase-Ras pathway had distinct impacts on survival; five genomic alterations independently doubled mortality. These findings create avenues for personalized treatment in LCINS.Citation
Zhang T, Joubert P, Ansari-Pour N, Zhao W, Hoang PH, Lokanga R, et al. Genomic and evolutionary classification of lung cancer in never smokers. Nat Genet. 2021 Sep;53(9):1348–59.Journal
Nature GeneticsDOI
10.1038/s41588-021-00920-0PubMed ID
34493867Additional Links
https://dx.doi.org/10.1038/s41588-021-00920-0Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41588-021-00920-0
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