BBB seminar: Stian Knappskog

Stian Knappskog
Department of Clinical Science, University of Bergen

Massive parallel sequencing technologies has allowed in-depth analyses of the genomic landscape of human cancers.

Applying such analyses on primary breast cancers, we have revealed varying levels of intratumour heterogeneity. We have used mutation patterns and heterogeneity to track the molecular evolutionary history of each tumour. Contrasting some other cancer types, no strict temporal order of mutational events was evident in breast cancer, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumours and late in others.

Performing similar analyses on metastatic breast cancers, several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumours, but continue to acquire mutations. Most mutations occurring in the metastatic setting are caused by the same mutational processes as in the primary tumour. Most distant metastases also acquire “driver” mutations not seen in the primary tumour, drawing from a wider repertoire of cancer genes than the “drivers” occurring in primary disease.

Currently, we are applying analyses of intratumour heterogeneity as a basis for assessments of subclonal dynamics during chemotherapy treatment of breast cancers. This provides a new strategy for identification of predictive biomarkers.

Chairperson: Nils Halberg, Department of Biomedicine