Novel approaches for the molecular classification of prostate cancer

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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Molecular classification of green tea catechin-sensitive and green tea catechin-resistant prostate cancer in the TRAMP mice model by quantitative real-time PCR gene profiling

Carcinogenesis ◽

10.1093/carcin/bgi287 ◽

2005 ◽

Vol 27 (5) ◽

pp. 1047-1053 ◽

Cited By ~ 19

Author(s):

Maurizio Scaltriti ◽

Lucia Belloni ◽

Andrea Caporali ◽

Pierpaola Davalli ◽

Daniel Remondini ◽

...

Keyword(s):

Prostate Cancer ◽

Green Tea ◽

Real Time Pcr ◽

Molecular Classification ◽

Gene Profiling ◽

Quantitative Real Time Pcr ◽

Mice Model ◽

Green Tea Catechin ◽

Tramp Mice

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Molecular classification of prostate cancer using curated expression signatures

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1117029108 ◽

2011 ◽

Vol 108 (52) ◽

pp. 21276-21281 ◽

Cited By ~ 134

Author(s):

E. K. Markert ◽

H. Mizuno ◽

A. Vazquez ◽

A. J. Levine

Keyword(s):

Prostate Cancer ◽

Molecular Classification

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Does the molecular classification of breast cancer point the way for biomarker identification in prostate cancer?

World Journal of Clinical Urology ◽

10.5410/wjcu.v5.i2.80 ◽

2016 ◽

Vol 5 (2) ◽

pp. 80

Author(s):

William J F Green ◽

Graham Ball ◽

Des Powe

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Molecular Classification ◽

Biomarker Identification ◽

The Way

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Genome-Based Classification and Therapy of Prostate Cancer

Diagnostics ◽

10.3390/diagnostics8030062 ◽

2018 ◽

Vol 8 (3) ◽

pp. 62 ◽

Cited By ~ 5

Author(s):

Arlou Angeles ◽

Simone Bauer ◽

Leonie Ratz ◽

Sabine Klauck ◽

Holger Sültmann

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Molecular Classification ◽

Therapy Resistance ◽

Clinical Practices ◽

Molecular Alterations ◽

The Past ◽

Cancer Genomes ◽

Treatment Concepts

In the past decade, multi-national and multi-center efforts were launched to sequence prostate cancer genomes, transcriptomes, and epigenomes with the aim of discovering the molecular underpinnings of tumorigenesis, cancer progression, and therapy resistance. Multiple biological markers and pathways have been discovered to be tumor drivers, and a molecular classification of prostate cancer is emerging. Here, we highlight crucial findings of these genome-sequencing projects in localized and advanced disease. We recapitulate the utility and limitations of current clinical practices to diagnosis, prognosis, and therapy, and we provide examples of insights generated by the molecular profiling of tumors. Novel treatment concepts based on these molecular alterations are currently being addressed in clinical trials and will lead to an enhanced implementation of precision medicine strategies.

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