Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

Molecular Cancer

Research

Marcel Smid¹  Zhenlin Ju²  Christopher I Amos³  Musaffe Tuna³  Gordon B Mills⁴ 

[1] Department of Medical Oncology, Erasmus Medical Center – Daniel den Hoed Cancer Center, and Cancer Genomics Center, Rotterdam, The Netherlands;Departments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;Departments of Epidemiology, Unit 1340, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030-4009, Houston, TX, USA;Departments of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;

关键词: Acquired uniparental disomy;    Ovarian cancer;    Overall survival;    Recurrence-free survival;   

DOI  :  10.1186/s12943-015-0289-1

 received in 2014-09-25, accepted in 2015-01-04,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAcquired 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.MethodsWe 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.ResultsWe 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).ConclusionsaUPD is a common event and some recurrent loci are associated with a poor outcome for patients with serous ovarian cancer.

【 授权许可】

CC BY   
© Tuna et al.; licensee BioMed Central. 2015