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  • Nunes, Luís,1995-Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab (author)

Molecular characterization of a large unselected cohort of metastatic colorectal cancers in relation to primary tumor location, rare metastatic sites and prognosis

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020
  • electronicrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:uu-423562
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-423562URI
  • https://doi.org/10.1080/0284186X.2019.1711169DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • Background: We have reported that BRAF V600E mutations and microsatellite instability-high (MSI-H) are more prevalent in a population-based cohort of metastatic colorectal cancer (mCRC) patients than has been reported from clinical trials or hospital-based patient groups. The aim was to explore if other mutations in mCRC differ in prevalence between these cohorts in relation to mismatch repair status and primary tumor location and if presence of bone or brain metastases is associated with any mutations.Material and methods: A population-based cohort of 798 mCRC patients from three regions in Scandinavia was used. Forty-four cancer related genes were investigated in a custom designed Ampliseq hotspot panel. Differences in survival were analyzed using the Kaplan–Meier estimator and the Cox regression analysis.Results: Determination of mutations was possible in 449/501 patients for 40/44 genes. Besides BRAF V600E, seen in 19% of the tumors, none of the other mutations appeared more prevalent than in trial cohorts. BRAF V600E and MSI-H, seen in 8%, were associated with poor prognosis as was right-sided primary tumor location (39%) when compared to left-sided and rectum together; however, in a multivariable regression, only the BRAF mutation retained its statistical significance. No other mutations were associated with poor prognosis. ERBB2 alterations were more common if bone metastases were present at diagnosis (17% vs. 4%, p = .011). No association was found for brain metastases. Fifty-two percent had an alteration that is treatable with an FDA-approved targeted therapy, chiefly by EGFR-inhibitor for RAS wild-type and a check-point inhibitor for MSI-H tumors.Conclusions: Right-sided tumor location, BRAF V600E mutations, but no other investigated mutation, and MSI-H are more commonly seen in an unselected cohort than is reported from clinical patient cohorts, likely because they indicate poor prognosis. Half of the patients have a tumor that is treatable with an already FDA-approved targeted drug for mCRC.

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  • Aasebø, KristineUniv Bergen, Dept Clin Sci, Bergen, Norway (author)
  • Mathot, Lucy (author)
  • Ljungström, Viktor,1986-Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)viklj600 (author)
  • Edqvist, Per-HenrikUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)peedq227 (author)
  • Sundström, MagnusUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)magnsund (author)
  • Dragomir, AncaUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ Hosp, Dept Pathol, Uppsala, Sweden(Swepub:uu)ancadrag (author)
  • Pfeiffer, PerOdense Univ Hosp, Dept Oncol, Odense, Denmark (author)
  • Ameur, AdamUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)adame789 (author)
  • Pontén, FredrikUppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)fredpont (author)
  • Mezheyeuski, ArturUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)artme913 (author)
  • Sorbye, HalfdanUniv Bergen, Dept Clin Sci, Bergen, Norway; Haukeland Hosp, Dept Oncol, Bergen, Norway (author)
  • Sjöblom, TobiasUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)tobisjob (author)
  • Glimelius, BengtUppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)bengglim (author)
  • Uppsala universitetExperimentell och klinisk onkologi (creator_code:org_t)

Related titles

  • In:Acta Oncologica59:4, s. 417-4260284-186X1651-226X

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