Whole-exome sequencing demonstrates recurrent somatic copy number alterations and sporadic mutations in specialized stromal tumors of the prostate

Hum Pathol. 2018 Jun:76:9-16. doi: 10.1016/j.humpath.2017.12.004. Epub 2017 Dec 16.

Abstract

In a previous array comparative genomic hybridization study, we detected common deletions of chromosomes 13 and 14 in prostatic stromal sarcoma and stromal tumor of uncertain malignant potential (STUMP). In this study, we performed whole-exome sequencing (WES) and fluorescence in situ hybridization to explore somatic mutations in 1 low-grade stromal sarcoma, 1 high-grade stromal sarcoma, and 12 STUMPs including 5 cases of degenerative atypia type, 1 myxoid type, 1 phyllodes type, and 5 cases of recently described round cell type. WES was successful on 13 cases that revealed frequent somatic copy number alterations including losses of chromosomes 13 (11 cases), 14 (11 cases), and 1p (9 cases), and partial or complete loss of chromosome 10 (7 cases). Fluorescence in situ hybridization was done on 9 cases and showed compatible chromosome 13 copy numbers with the WES results. STUMPs and the low-grade stromal sarcoma carried moderate tumor mutation burdens that ranged from 1.23 to 7.24 mutations per megabase, while the high-grade stromal sarcoma harbored a significantly higher mutation burden (11.55 mutations per megabase). Sporadic somatic mutations were observed, but no recurrent driver mutations could be discerned. In conjunction with prior array comparative genomic hybridization, we have demonstrated the consistent gene dosage profiles that support the clonal nature and the concept of specialized stromal tumors of the prostate as a distinctive tumor entity.

Keywords: Fluorescence in situ hybridization; Prostatic stromal tumor of uncertain malignant potential; Somatic copy number alteration; Stromal sarcoma; Whole-exome sequencing.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • DNA Copy Number Variations*
  • DNA Mutational Analysis
  • Exome Sequencing*
  • Gene Dosage*
  • Genetic Predisposition to Disease
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mutation*
  • Neoplasm Grading
  • Phenotype
  • Prostatic Hyperplasia / genetics*
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Stromal Cells / chemistry*
  • Stromal Cells / pathology

Substances

  • Biomarkers, Tumor

Supplementary concepts

  • Prostatic stromal proliferation of uncertain malignant potential