Germline copy number variations are associated with breast cancer risk and prognosis.
Germline copy number variations are associated with breast cancer risk and prognosis.
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DOI：
10.1038/s41598-017-14799-7
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发表时间：
2017-11-07
影响因子：
4.6
通讯作者：
Damaraju S
中科院分区：
文献类型：
--
作者：
Kumaran M;Cass CE;Graham K;Mackey JR;Hubaux R;Lam W;Yasui Y;Damaraju S
乳腺癌是女性最常见的癌症之一，其易感性与基因、生活方式和环境因素有关。拷贝数变异(CNV)是一种结构性DNA变异，通过基因剂量效应或顺式调控导致不同的表型。在这项研究中，我们的目标是确定胚系CNV与乳腺癌易感性及其与预后的相关性。我们用人类Affymetrix SNP-6基因芯片对422例患者和348例对照进行了全基因组CNV基因分型。人群分层主成分分析显示高加索血统中有84个异常值，366个病例和320个对照用于关联分析； >； 频率为10%的CNV和与蛋白编码基因重叠的CNV被认为与乳腺癌风险和预后相关。通过将拷贝数状态与乳腺肿瘤组织中的基因表达谱相关联，询问识别的CNV中的编码基因的基因剂量效应。我们确定了200个与乳腺癌相关的CNV(Q-Value <； 0.05)。其中21个CNV区(与22个基因重叠)也与预后相关。我们用TaqMan实验验证了与APOBEC3B和GSTM1基因重叠的有代表性的CNV。生殖系CNV对乳腺组织中的基因表达具有剂量效应。在这项研究中确定的候选CNV需要独立复制。
Breast cancer is one of the most common cancers among women, and susceptibility is explained by genetic, lifestyle and environmental components. Copy Number Variants (CNVs) are structural DNA variations that contribute to diverse phenotypes via gene-dosage effects or cis-regulation. In this study, we aimed to identify germline CNVs associated with breast cancer susceptibility and their relevance to prognosis. We performed whole genome CNV genotyping in 422 cases and 348 controls using Human Affymetrix SNP 6 array. Principal component analysis for population stratification revealed 84 outliers leaving 366 cases and 320 controls of Caucasian ancestry for association analysis; CNVs with frequency > 10% and overlapping with protein coding genes were considered for breast cancer risk and prognostic relevance. Coding genes within the CNVs identified were interrogated for gene- dosage effects by correlating copy number status with gene expression profiles in breast tumor tissue. We identified 200 CNVs associated with breast cancer (q-value < 0.05). Of these, 21 CNV regions (overlapping with 22 genes) also showed association with prognosis. We validated representative CNVs overlapping with APOBEC3B and GSTM1 genes using the TaqMan assay. Germline CNVs conferred dosage effects on gene expression in breast tissue. The candidate CNVs identified in this study warrant independent replication.
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影响因子：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1158/1055-9965.epi-10-0085
发表时间：
2010-04
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Azzato EM;Pharoah PD;Harrington P;Easton DF;Greenberg D;Caporaso NE;Chanock SJ;Hoover RN;Thomas G;Hunter DJ;Kraft P
通讯作者：
Kraft P
影响因子：
5.8
作者：
Fanale, Daniele;Iovanna, Juan Lucio;Russo, Antonio
通讯作者：
Russo, Antonio