Identification of novel deletion polymorphisms in breast cancer
Identification of novel deletion polymorphisms in breast cancer
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DOI：
10.3892/ijo_00000005
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发表时间：
2008-08-01
影响因子：
5.2
通讯作者：
Miki, Yoshio
中科院分区：
文献类型：
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作者：
Komatsu, Akira;Nagasaki, Koichi;Miki, Yoshio
乳腺癌是世界范围内女性最常见的癌症，长期以来人们一直知道多种基因重排与复杂的生物学和临床行为相关。此外，DNA序列的拷贝数变异（copy number variations，CNVs）在正常表型变异中占很大比例，并且可能在人类病理变异中起重要作用。在这项研究中，我们进行了高密度寡核苷酸阵列比较基因组杂交（CGH）分析在一系列乳腺癌细胞系，以确定新的纯合缺失位点。通过定量PCR（Q-PCR）对结果进行验证，筛选出REV 1 L、ZNF 14、NPAS 1和APOBEC 3B 4个基因。对30例显微切割的人乳腺肿瘤和配对的正常乳腺组织样本的分析表明，这些纯合性缺失是小规模的缺失多态性。血液来源的DNA中4个基因位点的拷贝数的变化表明，乳腺癌患者中包括纯合缺失和单拷贝变异的缺失频率高于健康女性。值得注意的是，APOBEC 3B的纯合缺失涉及外显子5的一部分，并且在一些患者中似乎是癌症特异性的，表明这是一种功能重要的结构变体。这些拷贝数的变化可能在乳腺癌中发挥重要作用，因此，阵列CGH分析有望为乳腺癌的遗传背景提供新的见解。
Breast cancer is the most frequent cancer in females worldwide and it has long been known that multiple genetic rearrangements correlate with complex biology and clinical behavior. In addition, copy number variations (CNVs) of DNA sequences account for a significant proportion of normal phenotypic variation and may have an important role in human pathological variation. In this study, we carried out a high-density oligonucleotide array comparative genomic hybridization (CGH) analyses in a series of breast cancer cell lines to identify novel homozygous deletion loci. The results were confirmed by quantitative PCR (Q-PCR) and 4 genes, the REV1L, ZNF14, NPAS1 and APOBEC3B genes, were selected. Analyses of 30 microdissected human breast tumors and paired normal mammary tissue samples indicated that these homozygous deletions are small-scale deletion polymorphisms. The variation in copy number at the loci of the 4 genes in blood-derived DNA demonstrated the frequency of deletions including homozygous deletions and single copy variants to be higher in breast cancer patients than healthy females. Notably, the homozygous deletion of APOBEC3B involved part of exon 5 and seemed to be cancer-specific in some patients, indicating that this is a functionally important structural variant. These copy number changes may play an important role in breast cancer and array-CGH analyses can thus be expected to provide new insight into the genetic background of breast cancer.