Eight mutational footprints emerge across 959 prostate cancer genomes
The Pan Prostate Cancer Group jointly analysed several kinds of genomic change in tumours from 959 donors and identified eight integrated mutational footprints. The footprints covered processes operating in 85% of primary prostate cancer genomes. Four were associated with a shorter time to metastasis. The retrospective genomic patterns do not constitute a validated clinical test that predicts metastatic timing for an individual patient.
Science··Morning
Four classes of genomic change entered one analysis
The Pan Prostate Cancer Group contributed tumour genomes from 959 donors to a joint analysis. The analysis placed complex structural-variant signatures and shifts in copy number alongside small insertions or deletions and single-base substitutions. Instead of leaving each class of change as a separate list, the method grouped processes that co-occurred in a tumour into integrated patterns. The dataset is based on primary prostate cancer samples. News-Medical reported the study independently, writing that cancer begins with errors in the DNA inside our cells and that those errors are often more complicated than a handful of mutated genes.[1], [2]
Eight footprints covered 85% of primary tumours
The analysis produced eight integrated mutational footprints that accounted for processes operating in 85% of primary prostate cancer genomes. Regional features of the genome strongly shaped their distribution. The most frequent influences included androgen receptor-mediated mutagenesis and stress during DNA replication. The coverage figure also shows that the same eight footprints were not sufficient for the remaining 15%.[1]
Four footprints were linked to shorter time to metastasis
Researchers found four of the footprints in 37% of the primary tumour samples and linked them statistically to less time before metastasis. One of the four included mutagenesis connected to reactive oxygen species. The association does not prove that this process initiated metastasis on its own. The footprints require testing in independent patient groups and measurement of whether they add information beyond existing clinical indicators.[1]
