uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
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.
Show others and affiliations
2019 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 10, p. 1540-1548Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2019. Vol. 25, no 10, p. 1540-1548
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-396656DOI: 10.1038/s41591-019-0595-zISI: 000489166700023PubMedID: 31591602OAI: oai:DiVA.org:uu-396656DiVA, id: diva2:1370175
Funder
EU, European Research Council, FP7-THESEUS-617844EU, European Research Council, 835297Available from: 2019-11-14 Created: 2019-11-14 Last updated: 2020-01-08Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Djureinovic, DijanaLa Fleur, LinneaBotling, JohanMicke, Patrick

Search in DiVA

By author/editor
Birkbak, Nicolai J.Papp, KrisztianDjureinovic, DijanaLa Fleur, LinneaBotling, JohanMicke, Patrick
By organisation
Clinical and experimental pathology
In the same journal
Nature Medicine
Cancer and OncologyClinical Laboratory Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 102 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf