Challenges in identifying candidate amplification targets in human cancers: chromosome 8q21 as a case study.
Challenges in identifying candidate amplification targets in human cancers: chromosome 8q21 as a case study.
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DOI：
10.1177/1947601912456287
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发表时间：
2012-02-01
期刊：
影响因子：
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通讯作者：
Peters, Gregory B
中科院分区：
文献类型：
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作者：
Byrne, Jennifer A;Chen, Yuyan;Peters, Gregory B
需要对癌症标本进行详细的基因组特征分析，以确定其失调导致肿瘤发生和/或肿瘤进展的所有基因。其中包括扩增靶基因，其致癌功能源于基因拷贝数增加时的过度表达，并且越来越多地作为治疗靶点和预测标记。我们提出，鉴定新的扩增靶基因正变得越来越具有挑战性，可能需要对绘制基因拷贝数变化和/或确定基因拷贝数与表达之间关系的多项研究进行比较分析。因此，我们回顾了阵列比较基因组杂交和单核苷酸多态性分析文献，以确定人类癌症中仅限于染色体8q21的拷贝数增加，这在乳腺癌中最为常见。我们确定了获得的区域之间的最小重叠区域，然后检查了哪些染色体8q21基因在个体研究中最常过度表达，或以其他方式支持。由于这些组合方法支持先前提出的扩增靶点TCEB1、TPD52和WWP1，因此，多个基因组研究的比较可以有效地预测候选基因扩增靶点，并优先考虑这些靶点进行进一步研究。
Detailed genomic characterization of cancer specimens is required to identify all genes whose dysregulation contributes to tumorigenesis and/or tumor progression. These include amplification target genes, whose oncogenic functions derive from their overexpression in response to increased gene copy number, and which increasingly serve as therapeutic targets and predictive markers. We propose that identifying novel amplification target genes is becoming more challenging, and may require the comparative analysis of multiple studies mapping gene copy number changes and/or defining associations between gene copy number and expression. We therefore reviewed the array comparative genomic hybridization and single nucleotide polymorphism profiling literature to identify copy number increases that were restricted to chromosome 8q21 in human cancers, which were reported most frequently in breast cancer. We determined the minimal regions of overlap between gained regions and then examined which chromosome 8q21 genes were most frequently overexpressed, or otherwise supported, in individual studies. As these combined approaches supported the previously proposed amplification targets TCEB1, TPD52, and WWP1, the comparison of multiple genomic studies may therefore effectively predict candidate gene amplification targets, and prioritize these for further study.