학술논문
Genomic and evolutionary classification of lung cancer in never smokers
Document Type
Article
Author
Zhang, Tongwu; Joubert, Philippe; Ansari-Pour, Naser; Zhao, Wei; Hoang, Phuc H.; Lokanga, Rachel; Moye, Aaron L.; Rosenbaum, Jennifer; Gonzalez-Perez, Abel; Martínez-Jiménez, Francisco; Castro, Andrea; Muscarella, Lucia Anna; Hofman, Paul; Consonni, Dario; Pesatori, Angela C.; Kebede, Michael; Li, Mengying; Gould Rothberg, Bonnie E.; Peneva, Iliana; Schabath, Matthew B.; Poeta, Maria Luana; Costantini, Manuela; Hirsch, Daniela; Heselmeyer-Haddad, Kerstin; Hutchinson, Amy; Olanich, Mary; Lawrence, Scott M.; Lenz, Petra; Duggan, Maire; Bhawsar, Praphulla M. S.; Sang, Jian; Kim, Jung; Mendoza, Laura; Saini, Natalie; Klimczak, Leszek J.; Islam, S. M. Ashiqul; Otlu, Burcak; Khandekar, Azhar; Cole, Nathan; Stewart, Douglas R.; Choi, Jiyeon; Brown, Kevin M.; Caporaso, Neil E.; Wilson, Samuel H.; Pommier, Yves; Lan, Qing; Rothman, Nathaniel; Almeida, Jonas S.; Carter, Hannah; Ried, Thomas; Kim, Carla F.; Lopez-Bigas, Nuria; Garcia-Closas, Montserrat; Shi, Jianxin; Bossé, Yohan; Zhu, Bin; Gordenin, Dmitry A.; Alexandrov, Ludmil B.; Chanock, Stephen J.; Wedge, David C.; Landi, Maria Teresa
Source
Nature Genetics; September 2021, Vol. 53 Issue: 9 p1348-1359, 12p
Subject
Language
ISSN
10614036; 15461718
Abstract
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 UBA1mutations, germline ARvariants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRASmutations 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 EGFRmutations (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.