[HTML][HTML] Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer

KT Carm, AM Hoff, AC Bakken, U Axcrona, K Axcrona… - Scientific reports, 2019 - nature.com
KT Carm, AM Hoff, AC Bakken, U Axcrona, K Axcrona, RA Lothe, RI Skotheim, M Løvf
Scientific reports, 2019nature.com
Prostate cancer is a highly heterogeneous disease and typically multiple distinct cancer foci
are present at primary diagnosis. Molecular classification of prostate cancer can potentially
aid the precision of diagnosis and treatment. A promising genomic classifier was published
by The Cancer Genome Atlas (TCGA), successfully classifying 74% of primary prostate
cancers into seven groups based on one cancer sample per patient. Here, we explore the
clinical usefulness of this classification by testing the classifier's performance in a multifocal …
Abstract
Prostate cancer is a highly heterogeneous disease and typically multiple distinct cancer foci are present at primary diagnosis. Molecular classification of prostate cancer can potentially aid the precision of diagnosis and treatment. A promising genomic classifier was published by The Cancer Genome Atlas (TCGA), successfully classifying 74% of primary prostate cancers into seven groups based on one cancer sample per patient. Here, we explore the clinical usefulness of this classification by testing the classifier’s performance in a multifocal context. We analyzed 106 cancer samples from 85 distinct cancer foci within 39 patients. By somatic mutation data from whole-exome sequencing and targeted qualitative and quantitative gene expression assays, 31% of the patients were uniquely classified into one of the seven TCGA classes. Further, different samples from the same focus had conflicting classification in 12% of the foci. In conclusion, the level of both intra- and interfocal heterogeneity is extensive and must be taken into consideration in the development of clinically useful molecular classification of primary prostate cancer.
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