Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

Musaffe Tuna, Zhenlin Ju, Marcel Smid, Christopher I. Amos, Gordon B. Mills

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient outcomes. Methods: We analyzed single nucleotide polymorphism (SNP) array-based genotyping data on 532 SOC specimens from The Cancer Genome Atlas database to identify aUPD regions. Cox univariate regression and Cox multivariate proportional hazards analyses were performed for survival analysis. Results: We found that 94.7% of SOC samples harbored aUPD; the most common aUPD regions were in chromosomes 17q (76.7%), 17p (39.7%), and 13q (38.3%). In Cox univariate regression analysis, two independent regions of aUPD on chromosome 17q (A and C), and whole-chromosome aUPD were associated with shorter overall survival (OS), and five regions on chromosome 17q (A, D-G) and BRCA1 were associated with recurrence-free survival time. In Cox multivariable proportional hazards analysis, whole-chromosome aUPD was associated with shorter OS. One region of aUPD on chromosome 22q (B) was associated with unilateral disease. A statistically significant association was found between aUPD at TP53 loci and homozygous mutation of TP53 (p < 0.0001). Conclusions: aUPD is a common event and some recurrent loci are associated with a poor outcome for patients with serous ovarian cancer.

Original languageEnglish (US)
Article number29
JournalMolecular Cancer
Volume14
Issue number1
DOIs
StatePublished - Feb 3 2015
Externally publishedYes

Keywords

  • Acquired uniparental disomy
  • Ovarian cancer
  • Overall survival
  • Recurrence-free survival

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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