Genomic and evolutionary classification of lung cancer in never smokers
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 sm...
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Published in | Nature genetics Vol. 53; no. 9; pp. 1348 - 1359 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.09.2021
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
Whole-genome sequencing of lung cancer in never smokers identifies different copy number subtypes and shows a lack of tobacco smoking signatures, even in cases exposed to secondhand smoke. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceptualization, MTL, TZ; Methodology, TZ, DCW, JS, BZ, NA-P, NL-B, BZ, SHW, YP, HC, TR, DS, DAG, LBA, MTL; Formal Analysis, TZ, NA-P, WZ, PHH, RL, AG, FM, AC, IP, JS, JK, NS, LJK, AMAI, BO, AK, AM, CFK; Laboratory work, AH, NC, JC, KB; Pathology work: MO, SML, MD, PL, PD, JDA; Resources, PJ, YB, PH, DC, ACP, LAM, BEGR, MBS, NEC, ML, SJC; Data Curation, MK, LM, JR; Writing – Original Draft, TZ, MTL; Writing – Review & Editing, DCW, SJC, YB, QL, NR, MG-C, DAG, LBA, NL-B, BZ, JS, TZ, PHH, MTL; Visualization, all authors; Supervision, MTL. Author Contributions |
ISSN: | 1061-4036 1546-1718 1546-1718 |
DOI: | 10.1038/s41588-021-00920-0 |