The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
The genomic landscape of TP53 and p53 annotated high grade ovarian serous carcinomas from a defined founder population associated with patient outcome.
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DOI：
10.1371/journal.pone.0045484
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tonin PN
中科院分区：
文献类型：
--
作者：
Wojnarowicz PM;Oros KK;Quinn MC;Arcand SL;Gambaro K;Madore J;Birch AH;de Ladurantaye M;Rahimi K;Provencher DM;Mes-Masson AM;Greenwood CM;Tonin PN
高级别卵巢浆液性癌（HGSC）的特征是TP 53突变和染色体异常的非随机模式，其中TP 53突变的性质可能与临床结果相关。然而，尚未探索来自人口统计学定义的人群的HGSC中发生的常见体细胞基因组事件的频率。全基因组SNP阵列，TP 53突变，基因和蛋白质表达分析进行了评估，在87个确认HGSC样本与临床相关的法裔加拿大人，人口表现出强烈的创始人效应，并与独立的报告描述了类似的分析结果进行了比较，从加拿大人口。在91%的HGSC中鉴定出TP 53突变。在超过50%的TP 53突变阳性HGSC中观察到的异常涉及3q、8 q和20 q的增加，以及4 q、5 q、6 q、8 p、13 q、16 q、17 p、17 q、22 q和Xp的丢失。近400个区域的非重叠扩增或缺失被确定，其中178个扩增和98个缺失涉及已知的基因。与p53蛋白缺失亚组相比，突变型p53蛋白表达亚组的总体生存期和无病生存期显著延长。有趣的是，基因组景观的比较分析显示，与p53蛋白空亚组相比，表达突变型p53蛋白的亚组中涉及1 q，8 q和12 p间隔的增益显着富集。虽然研究结果表明，TP 53突变的频率和在法裔加拿大人样本中观察到的基因组景观类似于那些报告的样本从ESTA人群，有差异的幅度全球增益/损失的特定染色体臂和扩增和删除的频谱涉及焦点区域在个别样品。我们比较基因组分析的结果也支持HGSC之间可能存在生物学差异的观点，这些差异可能与TP 53突变的性质有关。
High-grade ovarian serous carcinomas (HGSC) are characterized by TP53 mutations and non-random patterns of chromosomal anomalies, where the nature of the TP53 mutation may correlate with clinical outcome. However, the frequency of common somatic genomic events occurring in HGSCs from demographically defined populations has not been explored. Whole genome SNP array, and TP53 mutation, gene and protein expression analyses were assessed in 87 confirmed HGSC samples with clinical correlates from French Canadians, a population exhibiting strong founder effects, and results were compared with independent reports describing similar analyses from unselected populations. TP53 mutations were identified in 91% of HGSCs. Anomalies observed in more than 50% of TP53 mutation-positive HGSCs involved gains of 3q, 8q and 20q, and losses of 4q, 5q, 6q, 8p, 13q, 16q, 17p, 17q, 22q and Xp. Nearly 400 regions of non-overlapping amplification or deletion were identified, where 178 amplifications and 98 deletions involved known genes. The subgroup expressing mutant p53 protein exhibited significantly prolonged overall and disease-free survival as compared with the p53 protein null subgroup. Interestingly, a comparative analysis of genomic landscapes revealed a significant enrichment of gains involving 1q, 8q, and 12p intervals in the subgroup expressing mutant p53 protein as compared with the p53 protein null subgroup. Although the findings show that the frequency of TP53 mutations and the genomic landscapes observed in French Canadian samples were similar to those reported for samples from unselected populations, there were differences in the magnitude of global gains/losses of specific chromosomal arms and in the spectrum of amplifications and deletions involving focal regions in individual samples. The findings from our comparative genomic analyses also support the notion that there may be biological differences between HGSCs that could be related to the nature of the TP53 mutation.
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影响因子：
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作者：
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通讯作者：
Tonin PN
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