The Genomics of Prostate Cancer: A Historic Perspective

Abstract

The genomics of prostate cancer (PCA) has been difficult to study compared with some other cancer types for a multitude of reasons, despite significant efforts since the early 1980s. Overcoming some of these obstacles has paved the way for greater insight into the genomics of PCA. The advent of high-throughput technologies coming from the initial use of microsatellite and oligonucleotide probes gave rise to techniques like comparative genomic hybridization (CGH). With the introduction of massively parallel genomic sequencing, referred to as next-generation sequencing (NGS), a deeper understanding of cancer genomics in general has occurred. Along with these technologic advances, there has been the development of computational biology and statistical approaches to address novel large data sets characterized by single base resolution. This review will provide a historic perspective of PCA genomics with an emphasis on the cardinal mutations and alterations observed to be consistently seen in PCA for both hormone-naïve localized PCA and castration-resistant prostate cancer (CRPC). There will be a focus on alterations that have the greatest potential to play a role in disease progression and therapy management.

PARP inhibition in prostate cancer

“…Prostate cancer is characterized by a high degree of genomic instability leading to DNA breaks that are insufficiently repaired by the cellular DNA damage repair machinery 5‐7 . BRCA1 and BRCA2 are functionally and structurally different but their gene products function together in the error‐free repair of DNA double strand breaks known as homologous recombination‐mediated repair (HRR) 8 .…”

The Genomic Landscape of Prostate Cancer Brain Metastases

“…Unlike some other common solid tumors, PCa has more somatic copy number alterations than point mutations 17 . To obtain a more complete picture of potential pathways altered in the PCBM, we interrogated the WES data for somatic copy number alterations (SCNA) in the PCBM cohort and compared our findings with the CRPC500 cohort (Supplementary loss in PCBM, suggesting early driver events.…”

Generation of Whole-Genome Sequencing Data for Comparing Primary and Castration-Resistant Prostate Cancer

“…Understanding the molecular characteristics of the development of CRPC will help identify high-risk PC patients and develop novel therapeutic strategies to block the progression of CRPC. We generated a set of WGS data, consisting of eight PC samples containing four pairs of primary PC and CRPC samples from the same patient, because genetic mutations have the greatest potential to play a role in the progression of PC and CRPC and the therapeutic management of CRPC [ 16 , 17 ]. By comparing primary PC and its paired CRPC, many somatic mutations that were significantly associated with the development of CRPC were identified, including TP53 and KMT2C, which are known to be involved in the progression of PC [ 16 , 17 ].…”

“…We generated a set of WGS data, consisting of eight PC samples containing four pairs of primary PC and CRPC samples from the same patient, because genetic mutations have the greatest potential to play a role in the progression of PC and CRPC and the therapeutic management of CRPC [ 16 , 17 ]. By comparing primary PC and its paired CRPC, many somatic mutations that were significantly associated with the development of CRPC were identified, including TP53 and KMT2C, which are known to be involved in the progression of PC [ 16 , 17 ]. We hope that our whole-genome sequence data of the four paired PC and CRPC tissues will be utilized by many researchers to understand the progression of PC and the resistance to androgen deprivation therapy.…”