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A clonal expression biomarker associates with lung cancer mortality
UCL, Inst Canc, Canc Res UK Lung Canc Ctr Excellence, Paul OGorman Bldg, London, England;UCL, Inst Canc, Bill Lyons Informat Ctr, Paul OGorman Bldg, London, England;Francis Crick Inst, Canc Evolut & Genome Instabil Lab, London, England.
UCL, Inst Canc, Canc Res UK Lung Canc Ctr Excellence, Paul OGorman Bldg, London, England;Francis Crick Inst, Canc Evolut & Genome Instabil Lab, London, England;Aarhus Univ, Dept Mol Med, Aarhus, Denmark;Aarhus Univ, Bioinformat Res Ctr, Aarhus, Denmark.ORCID-id: 0000-0003-1613-9587
UCL, Inst Canc, Canc Res UK Lung Canc Ctr Excellence, Paul OGorman Bldg, London, England;UCL, Inst Canc, Bill Lyons Informat Ctr, Paul OGorman Bldg, London, England;Francis Crick Inst, Canc Evolut & Genome Instabil Lab, London, England.
UCL, Inst Canc, Canc Res UK Lung Canc Ctr Excellence, Paul OGorman Bldg, London, England;Francis Crick Inst, Canc Evolut & Genome Instabil Lab, London, England.
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2019 (Engelska)Ingår i: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, nr 10, s. 1540-1548Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage(1). Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types(2-6). Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.

Ort, förlag, år, upplaga, sidor
2019. Vol. 25, nr 10, s. 1540-1548
Nationell ämneskategori
Cancer och onkologi Klinisk laboratoriemedicin
Forskningsämne
Patologi
Identifikatorer
URN: urn:nbn:se:uu:diva-396656DOI: 10.1038/s41591-019-0595-zISI: 000489166700023PubMedID: 31591602OAI: oai:DiVA.org:uu-396656DiVA, id: diva2:1370175
Forskningsfinansiär
EU, Europeiska forskningsrådet, FP7-THESEUS-617844EU, Europeiska forskningsrådet, 835297Tillgänglig från: 2019-11-14 Skapad: 2019-11-14 Senast uppdaterad: 2020-01-08Bibliografiskt granskad

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Djureinovic, DijanaLa Fleur, LinneaBotling, JohanMicke, Patrick

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