Interfocal heterogeneity of prostate cancer

Prostate cancer is the most common type of cancer, and there is a pressing demand for both prognostic and predictive biomarkers. Despite massive and long-lasting efforts, cancer researchers have not yet succeeded. Research from the group proves that the presence of multiple tumour foci with different molecular characteristics complicates the development of biomarkers, in particular if this inter-focal heterogeneity is not taken into account.

The majority of mutations are not shared among cancer foci within the same patient

By utilizing a multifocality oriented biobank, the research group has demonstrated that individual tumour foci from the same patient have completely separate sets of somatic mutations (Løvf et al., 2019) and gene expression patterns (Strømme et al., 2022). Furthermore, expression of biomarkers show similar inter-focal heterogeneity (Kidd et al., 2021), and altogether this challenges the clinical usefulness of molecular classification of primary prostate cancer (Carm et al., 2019). Thus, introduction of genomics-guided personalized medicine has to take information from all tumour foci into account. This is a challenging task when it comes to sampling from the patients. To overcome this, the research group studies how this heterogeneity can be recapitulated in liquid biopsies (the cell free DNA [cfDNA] fraction of plasma). Also, for monitoring of prostate cancer, the group now tests whether mutation detection from cfDNA can inform on which of the original tumour foci that caused the disease relapse. The idea is that this can inform back to the primary situation, to enable development of improved prognostic biomarkers which will be informative for future patients with localized prostate cancer.

Publications

Carm KT, Johannessen B, Bogaard M, Bakken AC, Maltau AMV, Hoff AM, Axcrona U, Axcrona K, Lothe RA, and Skotheim RI (2023). Somatic mutations reveal complex metastatic seeding from multifocal primary prostate cancer. Int. J. Cancer 152(5): 945-51

Kidd SG*, Bogaard M*, Carm KT, Bakken AC, Maltau AMV, Løvf M, Lothe RA, Axcrona K, Axcrona U**, and Skotheim RI** (2022). In situ expression of ERG protein in the context of tumor heterogeneity identifies prostate cancer patients with inferior prognosis. Mol. Oncol. 16(15): 2810-22 Shared *first/**senior authors

Strømme JM, Johannessen B, Kidd SG, Bogaard M, Carm KT, Zhang X, Sveen A, Mathelier A, Lothe RA, Axcrona U, Axcrona K, and Skotheim RI (2022). Expressed prognostic biomarkers for primary prostate cancer independent of multifocality and transcriptome heterogeneity. Cancer Gene Therapy 29(8-9): 1276-84

Kidd SG*, Carm KT*, Bogaard M, Olsen LG, Bakken AC, Løvf M, Lothe RA, Axcrona K, Axcrona U, and Skotheim RI (2021). High expression of SChLAP1 in primary prostate cancer is an independent predictor of biochemical recurrence, despite substantial heterogeneity. Neoplasia 23(6): 634-41 *Equal contribution

Carm KT, Hoff AM, Bakken AC, Axcrona U, Axcrona K, Lothe RA, Skotheim RI*, and Løvf M (2019). The clinical usefulness of molecular classification of primary prostate cancer is challenged by interfocal heterogeneity. Scientific Reports 9: 13579 *Corresponding author

Løvf M, Zhao S, Axcrona U, Johannessen B, Bakken AC, Carm KT, Hoff AM, Myklebost O, Meza-Zepeda LA, Lie AK, Axcrona K, Lothe RA, and Skotheim RI (2019). Multifocal primary prostate cancer exhibits high degree of genomic heterogeneity. European Urology, 75(3): 498-505