Project group leaders Anita Sveen and Bjarne Johannessen at Department of Molecular Oncology at the Institute for Cancer Research are 1st and 2nd authors of a major work presenting the ”expressed mutation dose” as a determinant of the functional consequences of mutations in colorectal cancer.
Integrated whole-exome and RNA sequencing at allele-specific resolution showed that the majority of somatic cancer mutations are not expressed. However, mutation expression levels varied according to the target gene and mutation type, and cancer critical genes with point mutations had overexpression of the mutated compared to the wild-type allele. Mutation expression levels further correlated with downstream oncogenic signatures, and KRAS mutations were associated with a poor patient survival only when highly expressed. Proof-of-concept for a therapeutic relevance was shown by associations between allele-specific mutation expression levels and sensitivity to targeted anti-cancer agents in cell lines and patient derived tumor organoids.
Link to paper:
The expressed mutational landscape of microsatellite stable colorectal cancers
Anita Sveen, Bjarne Johannessen, Ina A. Eilertsen, Bård I. Røsok, Marie Gulla, Peter W. Eide, Jarle Bruun, Kushtrim Kryeziu, Leonardo A. Meza-Zepeda, Ola Myklebost, Bjørn A. Bjørnbeth, Rolf I. Skotheim, Arild Nesbakken & Ragnhild A. Lothe
Genome Medicine volume 13, Article number: 142 (2021)