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Genomic and evolutionary classification of lung cancer in never smokers

  1. Author:
    Zhang, Tongwu
    Joubert, Philippe
    Ansari-Pour, Naser
    Zhao, Wei
    Hoang, Phuc H.
    Lokanga, Rachel
    Moye, Aaron L.
    Rosenbaum, Jennifer
    Gonzalez-Perez, Abel
    Martinez-Jimenez, Francisco
    Castro, Andrea
    Muscarella, Lucia Anna
    Hofman, Paul
    Consonni, Dario
    Pesatori, Angela C.
    Kebede, Michael
    Li, Mengying
    Rothberg, Bonnie E. Gould
    Peneva, Iliana
    Schabath, Matthew B.
    Poeta, Maria Luana
    Costantini, Manuela
    Hirsch, Daniela
    Heselmeyer-Haddad, Kerstin
    Hutchinson,Amy
    Olanich, Mary
    Lawrence,Scott
    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
    Bosse, Yohan
    Zhu, Bin
    Gordenin, Dmitry A.
    Alexandrov, Ludmil B.
    Chanock, Stephen J.
    Wedge, David C.
    Landi, Maria Teresa

  2. Author Address

    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.Laval Univ, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.Univ Oxford, Big Data Inst, Nuffield Dept Med, Oxford, England.NCI, Canc Genom Sect, Ctr Canc Res, Bethesda, MD 20892 USA.Boston Childrens Hosp, Stem Cell Program, Boston, MA USA.Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA.Boston Childrens Hosp, Div Pulm Med, Boston, MA USA.Westat Corp, Rockville, MD USA.Barcelona Inst Sci & Technol, Inst Res Biomed Barcelona, Barcelona, Spain.Univ Calif San Diego, Dept Med, Div Med Genet, San Diego, CA 92103 USA.Fdn Ist Ricovero & Cura Carattere Sci Casa Sollie, Lab Oncol, San Giovanni Rotondo, Italy.Univ Cote Azur, Univ Hosp Federat OncoAge, Nice Hosp, Lab Clin & Expt Pathol, Nice, France.Fdn Ist Ricovero & Cura Carattere Sci Ca Granda O, Milan, Italy.Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.Yale New Haven Hlth, Smilow Canc Hosp, New Haven, CT USA.Yale Comprehens Canc Ctr, New Haven, CT USA.Univ Oxford, Wellcome Ctr Human Genet, Oxford, England.Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, England.H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.Univ Bari, Dept Biosci Biotechnol & Biopharmaceut, Bari, Italy.Ist Ricovero & Cura Carattere Sci, Regina Elena Natl Canc Inst, Dept Urol, Rome, Italy.Frederick Natl Lab Canc Res, Canc Genom Res Lab, Frederick, MD USA.Univ Calgary, Cumming Sch Med, Dept Pathol & Lab Med, Calgary, AB, Canada.NIEHS, Genome Integr & Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.NIEHS, Integrat Bioinformat Support Grp, POB 12233, Res Triangle Pk, NC 27709 USA.Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92103 USA.Univ Calif San Diego, Dept Bioengn, San Diego, CA 92103 USA.Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA.NCI, Ctr Canc Res, Dev Therapeut Branch, Bethesda, MD 20892 USA.NCI, Ctr Canc Res, Lab Mol Pharmacol, Bethesda, MD 20892 USA.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain.Laval Univ, Dept Mol Med, Quebec City, PQ, Canada.Univ Manchester, Manchester Canc Res Ctr, Manchester, Lancs, England.
    1. Year: 2021
    2. Date: Sep
    3. Epub Date: 2021 09 06
  2. Journal: Nature genetics
  3. NATURE PORTFOLIO,
    1. 53
    2. 9
    3. Pages: 1348-1359
  5. Type of Article: Article
  6. ISSN: 1061-4036
  1. 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 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.

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External Sources

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  2. DOI: 10.1038/s41588-021-00920-0
  3. PMID: 34493867
  4. PMCID: PMC8432745
  5. View record in Web of Science®
  6. WOS: 000694666000014

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  1. Fiscal Year: FY2021-2022
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