Emerging paradigms in cancer genetics: some important findings from high-density single nucleotide polymorphism array studies.
Emerging paradigms in cancer genetics: some important findings from high-density single nucleotide polymorphism array studies.
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DOI：
10.1158/0008-5472.can-08-3543
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发表时间：
2009-02-01
期刊：
影响因子：
11.2
通讯作者：
Barany F
中科院分区：
文献类型：
--
作者：
Bacolod MD;Schemmann GS;Giardina SF;Paty P;Notterman DA;Barany F
高密度单核苷酸多态性(SNP)定位阵列已经确定了染色体特征，其对癌症易感性和进展的重要性尚未明确。有趣的是，正常体细胞的基因组(反映了组合的双亲生殖系贡献)通常包含长的纯合子伸展。这些染色体片段可以通过个体父母的共同祖先来解释，因此也可以被称为同源合子。几项研究将血缘关系与更高的癌症发病率联系在一起，表明自合性(血缘关系的基因组结果)可能是癌症易感性的一个因素。SNP阵列分析也在癌症基因组中确定了体细胞单亲二体(UPD)的染色体区域。这些染色体片段的特征是杂合性缺失(LOH)和正常拷贝数(2)，但在生殖系或正常体细胞基因组中不是纯合子的。在这篇综述中，我们还将讨论一个模型[癌症基因活性模型(CGAM)]，该模型可能解释自合性如何影响癌症易感性。CGAM还可以解释癌变过程中某些染色体异常(拷贝数增加、LOH和体细胞UPDS)的发生如何依赖于在这些染色体区域发现的重要癌症相关基因(癌基因和肿瘤抑制基因)的胚系基因型。
High-density single nucleotide polymorphism (SNP) mapping arrays have identified chromosomal features whose importance to cancer predisposition and progression is not yet clearly defined. Of interest is that the genomes of normal somatic cells (reflecting the combined parental germ-line contributions) often contain long homozygous stretches. These chromosomal segments may be explained by the common ancestry of the individual’s parents and thus may also be called autozygous. Several studies link consanguinity to higher rates of cancer, suggesting that autozygosity (a genomic consequence of consanguinity) may be a factor in cancer predisposition. SNP array analysis has also identified chromosomal regions of somatic uniparental disomy (UPD) in cancer genomes. These are chromosomal segments characterized by loss of heterozygosity (LOH) and a normal copy number (two) but which are not autozygous in the germ-line or normal somatic cell genome. In this review, we will also discuss a model [cancer gene activity model (CGAM)] that may explain how autozygosity influences cancer predisposition. CGAM can also explain how the occurrence of certain chromosomal aberrations (copy number gain, LOH, and somatic UPDs) during carcinogenesis may be dependent on the germ-line genotypes of important cancer-related genes (oncogenes and tumor suppressors) found in those chromosomal regions.