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Sökning: onr:"swepub:oai:lup.lub.lu.se:c4c11b09-799e-4535-b03e-f4b6e9eb4fbf" > Lung adenocarcinoma...

  • Gatenby, Robert A.H. Lee Moffitt Cancer Center & Research Institute (författare)

Lung adenocarcinomas without driver genes converge to common adaptive strategies through diverse genetic, epigenetic, and niche construction evolutionary pathways

  • Artikel/kapitelEngelska2024

Förlag, utgivningsår, omfång ...

  • 2024

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:c4c11b09-799e-4535-b03e-f4b6e9eb4fbf
  • https://lup.lub.lu.se/record/c4c11b09-799e-4535-b03e-f4b6e9eb4fbfURI
  • https://doi.org/10.1007/s12032-024-02344-2DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Somatic evolution selects cancer cell phenotypes that maximize survival and proliferation in dynamic environments. Although cancer cells are molecularly heterogeneous, we hypothesized convergent adaptive strategies to common host selection forces can be inferred from patterns of epigenetic and genetic evolutionary selection in similar tumors. We systematically investigated gene mutations and expression changes in lung adenocarcinomas with no common driver genes (n = 313). Although 13,461 genes were mutated in at least one sample, only 376 non-synonymous mutations evidenced positive evolutionary selection with conservation of 224 genes, while 1736 and 2430 genes exhibited ≥ two-fold increased and ≥ 50% decreased expression, respectively. Mutations under positive selection are more frequent in genes with significantly altered expression suggesting they often “hardwire” pre-existing epigenetically driven adaptations. Conserved genes averaged 16-fold higher expression in normal lung tissue compared to those with selected mutations demonstrating pathways necessary for both normal cell function and optimal cancer cell fitness. The convergent LUAD phenotype exhibits loss of differentiated functions and cell–cell interactions governing tissue organization. Conservation with increased expression is found in genes associated with cell cycle, DNA repair, p53 pathway, epigenetic modifiers, and glucose metabolism. No canonical driver gene pathways exhibit strong positive selection, but extensive down-regulation of membrane ion channels suggests decreased transmembrane potential may generate persistent proliferative signals. NCD LUADs perform niche construction generating a stiff, immunosuppressive microenvironment through selection of specific collagens and proteases. NCD LUADs evolve to a convergent phenotype through a network of interconnected genetic, epigenetic, and ecological pathways.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Luddy, Kimberly A.H. Lee Moffitt Cancer Center & Research Institute (författare)
  • Teer, Jamie K.H. Lee Moffitt Cancer Center & Research Institute (författare)
  • Berglund, AndersH. Lee Moffitt Cancer Center & Research Institute (författare)
  • Freischel, Audrey R.University of Texas at Austin (författare)
  • Carr, Ryan M.Mayo Clinic Minnesota (författare)
  • Lam, Amanda E.Case Western Reserve University (författare)
  • Pienta, Kenneth J.Johns Hopkins University (författare)
  • Amend, Sarah R.Johns Hopkins University (författare)
  • Austin, Robert H.Princeton University (författare)
  • Hammarlund, Emma U.Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Molekylär evolution,Forskargrupper vid Lunds universitet,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Molecular Evolution,Lund University Research Groups(Swepub:lu)med-ehd (författare)
  • Cleveland, John L.H. Lee Moffitt Cancer Center & Research Institute (författare)
  • Tsai, Kenneth Y.H. Lee Moffitt Cancer Center & Research Institute (författare)
  • Brown, Joel S.H. Lee Moffitt Cancer Center & Research Institute (författare)
  • H. Lee Moffitt Cancer Center & Research InstituteUniversity of Texas at Austin (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Medical Oncology41:61357-0560

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