The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.
The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.
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DOI：
10.1158/1055-9965.epi-16-0106
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Easton DF
中科院分区：
文献类型：
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作者：
Amos CI;Dennis J;Wang Z;Byun J;Schumacher FR;Gayther SA;Casey G;Hunter DJ;Sellers TA;Gruber SB;Dunning AM;Michailidou K;Fachal L;Doheny K;Spurdle AB;Li Y;Xiao X;Romm J;Pugh E;Coetzee GA;Hazelett DJ;Bojesen SE;Caga-Anan C;Haiman CA;Kamal A;Luccarini C;Tessier D;Vincent D;Bacot F;Van Den Berg DJ;Nelson S;Demetriades S;Goldgar DE;Couch FJ;Forman JL;Giles GG;Conti DV;Bickeböller H;Risch A;Waldenberger M;Brüske-Hohlfeld I;Hicks BD;Ling H;McGuffog L;Lee A;Kuchenbaecker K;Soucy P;Manz J;Cunningham JM;Butterbach K;Kote-Jarai Z;Kraft P;FitzGerald L;Lindström S;Adams M;McKay JD;Phelan CM;Benlloch S;Kelemen LE;Brennan P;Riggan M;O'Mara TA;Shen H;Shi Y;Thompson DJ;Goodman MT;Nielsen SF;Berchuck A;Laboissiere S;Schmit SL;Shelford T;Edlund CK;Taylor JA;Field JK;Park SK;Offit K;Thomassen M;Schmutzler R;Ottini L;Hung RJ;Marchini J;Amin Al Olama A;Peters U;Eeles RA;Seldin MF;Gillanders E;Seminara D;Antoniou AC;Pharoah PD;Chenevix-Trench G;Chanock SJ;Simard J;Easton DF
常见的癌症是通过一个多步骤的过程发展起来的，通常包括遗传易感性。多个机构之间的合作，以及来自多个来源的资金，使一种廉价的基因分型微阵列OncoArray得以开发。该阵列包括一个全基因组的主干，由230,000个标记最常见的遗传变异的SNPs组成，以及已知易感区域、测序实验的罕见变异、药物遗传标记和癌症相关特征的密集图谱。使用Illumina开发的一项新技术可以对OncoArray进行基因分型，以促进有效的基因分型。该联盟制定了选择SNPs进行研究、标记质量控制和血统分析的标准方法。该阵列在选定的地点进行基因分型，并使用预先指定的复制样本，以允许在中心之间和根据种族背景评估基因分型的准确性。肿瘤阵列联盟对447,705个样本进行了基因分型。共有494,763个SNPs通过了质量控制步骤，样本成功率为97%。参与的网站使用一组共同的标记和基于主成分分析的评分算法进行祖先分析。这些分析的结果将使研究人员能够识别新的易感基因座，对与单一或多个癌症相关的新的或已知的基因座进行精细绘制，评估癌症病因的重叠程度和已被确定为疾病特定风险的基因座的多效性影响，并联合模拟与遗传、环境和生活方式相关的暴露。正在进行的分析将阐明许多类型癌症的病因和风险评估。
Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Ongoing analyses will shed light on etiology and risk assessment for many types of cancer.