Genomic analysis of aggressive ductal adenocarcinoma of the prostate

Cancer Med. 2023 Apr;12(7):8445-8451. doi: 10.1002/cam4.5573. Epub 2022 Dec 26.

Abstract

Background: Genomic profile analysis using next-generation sequencing can potentially elucidate the pathogenesis of rare cancers. Ductal adenocarcinoma, a rare subtype of prostate cancer, has an aggressive nature. This is the first study to analyze the genomic profile of ductal adenocarcinoma in an Asian population.

Methods: We identified 12 patients newly diagnosed with ductal adenocarcinoma of the prostate at two hospitals, and nine patients (75.0%) had the pure type. Genomic assessment was performed using either the PleSSision testing platform or FoundationOne CDx.

Results: At least one genomic alteration occurred in 11 patients (91.7%), and the most frequently mutated gene was tumor suppressor protein p53 (TP53), which was found in six cases (50.0%). Alterations characteristic of this cohort were found in four cases (33.3%) of retinoblastoma transcriptional corepressor 1 (RB1), which was only observed in the pure type. Compared to previous study results, the frequency of genetic alterations in the phosphoinositide 3-kinase (PI3K) pathway (n = 3; 25.0%) and Wnt-β-catenin pathway (n = 5; 41.7%) was comparable, but no alterations in the DNA damage repair (DDR) pathway were observed. None of the patients presented high tumor mutation burden or microsatellite instability.

Conclusions: We found that the Asian cohort with ductal adenocarcinoma had actionable alterations, and a high frequency of alterations in TP53 and RB1 reflected the aggressive nature of the tumor. Genetic analysis using next-generation sequencing is expected to help elucidate the pathogenesis of ductal adenocarcinoma.

Keywords: ductal adenocarcinoma; next generation sequencing; retinoblastoma transcriptional corepressor 1 (RB1); tumor suppressor protein p53 (TP53).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma*
  • Genomics
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Male
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics
  • Prostate*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Phosphatidylinositol 3-Kinases
  • Tumor Suppressor Protein p53