Hesson L B, Cooper W N, Latif F
Department of Medical and Molecular Genetics, MRC Protein Phosphorylation Unit, College of Life Sciences, Sir James Black Centre, Dow Street, University of Dundee, Dundee, UK.
Oncogene. 2007 Nov 15;26(52):7283-301. doi: 10.1038/sj.onc.1210547. Epub 2007 May 28.
Deletions of the 3p21.3 region are a frequent and early event in the formation of lung, breast, kidney and other cancers. Intense investigation of allelic losses and the discovery of overlapping homozygous deletions in lung and breast tumour-cell lines have defined a minimal critical 120 kb deletion region containing eight genes and likely to harbor one or more tumour-suppressor genes (TSGs). The candidate genes are HYAL2, FUS1, Ras-associated factor 1 (RASSF1), BLU/ZMYND10, NPR2L, 101F6, PL6 and CACNA2D2. Recent research indicates that several of these genes can suppress the growth of lung and other tumour cells. Furthermore, some genes (RASSF1A and BLU/ZMYND10) are very frequently inactivated by non-classical mechanisms such as promoter hypermethylation resulting in loss of expression. These data indicate that the 120 kb critical deletion region at 3p21.3 may represent a TSG cluster with preferential inactivation of particular genes depending on tumour type. The eight genes within this region and their potential role in cancer will be the focus of this review.
3p21.3区域的缺失是肺癌、乳腺癌、肾癌和其他癌症形成过程中常见的早期事件。对肺癌和乳腺癌肿瘤细胞系中等位基因缺失的深入研究以及重叠纯合缺失的发现，确定了一个最小关键120 kb缺失区域，该区域包含八个基因，可能含有一个或多个肿瘤抑制基因（TSG）。候选基因包括透明质酸酶2（HYAL2）、FUS1、Ras相关因子1（RASSF1）、BLU/ZMYND10、NPR2L、101F6、PL6和CACNA2D2。最近的研究表明，这些基因中的几个可以抑制肺癌和其他肿瘤细胞的生长。此外，一些基因（RASSF1A和BLU/ZMYND10）经常通过非经典机制失活，如启动子高甲基化导致表达缺失。这些数据表明，3p21.3处的120 kb关键缺失区域可能代表一个TSG簇，特定基因的优先失活取决于肿瘤类型。该区域内的八个基因及其在癌症中的潜在作用将是本综述的重点。
