Amplification of different satellite-DNAs in prostate cancer

Nurul Aida Ariffen1, Antonio Augusto Ornellas2, Gilda Alves3

  • 1Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany; Laboratory, Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia.

PubMed

Insights

Prostate cancer (PCa) shows genomic instability with copy number variations in satellite-DNA sequences. Advanced PCa cases exhibit amplification of specific satellite DNA regions, linked to long-non-coding RNA expression.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Acquired copy number variations (CNVs) involving centromeric satellite-DNA sequences have been anecdotally observed in solid tumors.
  • Prostate cancer (PCa) is a common malignancy with known molecular cytogenetic aberrations.

Purpose of the Study:

  • To systematically screen for satellite-DNA sequence amplification in prostate cancer samples.
  • To investigate the association between satellite-DNA alterations and PCa progression.

Main Methods:

  • Systematic screening of 31 prostate cancer samples for satellite-DNA sequence amplification.
  • Analysis of PCa-typical genetic aberrations including TMPRSS2-ERG gene rearrangements and PTEN deletion.
  • Assessment of genomic instability across satellite-DNA regions, with a focus on the Y-chromosome.

Main Results:

  • Prostate cancer samples displayed genomic instability with chromosomal gains or losses in most tested satellite-DNA regions, notably the Y-chromosome (18/31 cases).
  • Five out of 12 advanced metastatic prostate cancer samples showed amplification of specific satellite DNA stretches (α-satellite DNA from chromosomes 2, 3, 4, 15, 20, and satellite-III DNAs D1Z1, DYZ1).
  • These amplified regions were detectable as blocks similar to homogenously staining regions.

Conclusions:

  • Prostate cancer exhibits significant genomic instability involving satellite-DNA sequences.
  • Amplification of specific satellite DNA regions occurs in advanced metastatic prostate cancer.
  • Findings support recent research on α-satellite DNA expression as long-non-coding RNAs in advanced cancers, particularly PCa.