Tuna Musaffe, Ju Zhenlin, Smid Marcel, Amos Christopher I, Mills Gordon B
Departments of Epidemiology, Unit 1340, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA.
Departments of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mol Cancer. 2015 Feb 3;14(1):29. doi: 10.1186/s12943-015-0289-1.
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.
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.
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).
aUPD is a common event and some recurrent loci are associated with a poor outcome for patients with serous ovarian cancer.
获得性单亲二体（aUPD）可导致肿瘤抑制基因或癌基因纯合。我们的目的是确定浆液性卵巢癌（SOC）中aUPD区域的频率和特征，并研究aUPD与临床特征和患者预后的关联。
我们分析了来自癌症基因组图谱数据库的532例SOC标本基于单核苷酸多态性（SNP）阵列的基因分型数据，以识别aUPD区域。进行Cox单因素回归和Cox多因素比例风险分析用于生存分析。
我们发现94.7%的SOC样本存在aUPD；最常见的aUPD区域位于17号染色体长臂（76.7%）、17号染色体短臂（39.7%）和13号染色体长臂（38.3%）。在Cox单因素回归分析中，17号染色体长臂上两个独立的aUPD区域（A和C）以及全染色体aUPD与总生存期（OS）缩短相关，17号染色体长臂上的五个区域（A、D - G）和BRCA1与无复发生存时间相关。在Cox多因素比例风险分析中，全染色体aUPD与较短的OS相关。22号染色体长臂上一个aUPD区域（B）与单侧疾病相关。在TP53基因座的aUPD与TP53纯合突变之间发现有统计学意义的关联（p < 0.0001）。
aUPD是一个常见事件，一些反复出现的基因座与浆液性卵巢癌患者的不良预后相关。
