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

Author:

Carm Kristina Totland,Hoff Andreas M.,Bakken Anne Cathrine,Axcrona Ulrika,Axcrona Karol,Lothe Ragnhild A.,Skotheim Rolf I.ORCID,Løvf Marthe

Abstract

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.

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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