Novel regions of amplification on 8q distinct from the MYC locus and frequently altered in oral dysplasia and cancer
Novel regions of amplification on 8q distinct from the MYC locus and frequently altered in oral dysplasia and cancer
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DOI：
10.1002/gcc.10294
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发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Lam, WL
中科院分区：
文献类型：
--
作者：
Garnis, C;Coe, BP;Lam, WL
旨在确定口腔癌关键改变的遗传学研究主要集中在肿瘤分析上，由于样本可用性和规模的限制，很少有此类研究使用早期口腔癌前病变（opl）。在这项研究中，我们使用随机扩增多态性DNA (RAPD)-PCR方法对微解剖的正常和发育不良细胞的DNA进行指纹鉴定，并在opl的8号染色体长臂上发现了两个复发性遗传改变，一个定位于MYC位点附近的8q22，另一个定位于8q24。我们构建了一个高分辨率的细菌人工染色体（BAC）比较基因组杂交阵列，该阵列由166个重叠的BAC克隆组成，从8q21到8q24约52 l。将口腔微解剖肿瘤的DNA与该阵列进行杂交，发现8q24位点发生改变，含有MYC的BAC扩增。引人注目的是，至少在8q22上发现了另外两个新的扩增区域。对93例口腔发育不良和肿瘤的微卫星分析证实了其中一个8q22位点的改变。D8S1830的杂合性缺失（LOH），定位于扩增区域之一，在opl和肿瘤中都观察到高频率。在37例D8S1830处LOH的病例中，23例（62%）在D8S1793处保留，这将1.6 Mbp的着丝点映射到MYC。这进一步支持了8q22的改变与MYC的不同。这些数据提高了MYC位点附近8q上其他致癌基因可能参与OPL疾病进展的可能性。(C) 2003 Wiley-Liss, Inc。
Genetic studies aimed at identifying key alterations in oral cancers have focused on analysis of tumors, with few such studies using early oral premalignant lesions (OPLs) because of limitations in both sample availability and size. In this study, we used a randomly amplified polymorphic DNA (RAPD)-PCR approach to fingerprint DNA from microdissected normal and dysplastic cells and identified two recurrent genetic alterations on the long arm of chromosome 8 in OPLs, one mapping to 8q22 and the other to 8q24 near the MYC locus. We constructed a high-resolution bacterial artificial chromosome (BAC) comparative genomic hybridization array consisting of 166 overlapping BAC clones that spans about 52 l from 8q21 to 8q24. Hybridization of DNA from microdissected oral tumors to the array revealed alteration at 8q24, with amplification of the BAC containing MYC. Strikingly, at least two other novel regions of amplification at 8q22 were identified. Microsatellite analysis of 93 oral dysplasias and tumors confirmed the presence of one of the alterations at 8q22. Loss of heterozygosity (LOH) at D8S1830, mapping within one of the regions of amplification, was observed in high frequency in both OPLs and tumors. Of the 37 cases with LOH at D8S1830, 23 (62%) showed retention at D8S1793, which maps 1.6 Mbp centromeric to MYC. This is further support for the alteration at 8q22 being distinct from MYC. These data raise the possibility of additional oncogenes on 8q near the MYC locus that are potentially involved in OPL disease progression. (C) 2003 Wiley-Liss, Inc.