Angeloni Debora
Superiore Sant'Anna and Institute of Clinical Physiology-National Research Council (IFC-CNR), Via Moruzzi 1, 56124 Pisa, Italy.
Brief Funct Genomic Proteomic. 2007 Mar;6(1):19-39. doi: 10.1093/bfgp/elm007. Epub 2007 May 24.
Epithelial cancers inflict a heavy human and social burden. It was estimated [Tyczynski JE, Bray F, Parkin DM. Lung cancer in Europe in 2000: epidemiology, prevention, and early detection. Lancet Oncol 2003;4:45-55 (Review)] that in Europe, in the year 2000, 347 000 persons died of lung cancer alone, the deadliest cancer disease. Loss of heterozygosity and large homozygous deletions of the human chromosome region 3p21 are especially frequent in epithelial cancers of several organs. In fact, 3p21 is a very peculiar region of the genome harbouring, tightly clustered, several types of cancer-causing genes (CCG) (Lerman MI, Minna JD. The 630 kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumour suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res 2000;60:6116-33). Current results show that, unlike it was thought initially, many tumour suppressor genes (TSG) are located close by even in small genomic regions. They may be involved, perhaps with varying role, in different types of tumour, and may be influenced by the genetic background of different human populations as well as by environmental pollutants (cigarette smoking, professional exposure). This review will discuss methods of molecular analysis of genomic deletions to uncover CCG at 3p21, will summarize the present knowledge regarding the TSGs located in this region, and will describe a possible model of epithelial cancer pathogenesis.
上皮癌给人类和社会带来了沉重负担。据估计[泰钦斯基JE、布雷F、帕金DM。2000年欧洲的肺癌：流行病学、预防和早期检测。《柳叶刀肿瘤学》2003年；4：45 - 55（综述）]，在2000年的欧洲，仅死于肺癌这一致命癌症疾病的人数就达34.7万。人类染色体区域3p21的杂合性缺失和大的纯合缺失在多个器官的上皮癌中尤为常见。事实上，3p21是基因组中一个非常特殊的区域，紧密聚集着几种类型的致癌基因（CCG）（勒曼MI、明纳JD。人类染色体3p21.3上630kb的肺癌纯合缺失区域：常驻候选肿瘤抑制基因的鉴定和评估。国际肺癌染色体3p21.3肿瘤抑制基因联盟。《癌症研究》2000年；60：6116 - 33）。目前的研究结果表明，与最初的想法不同，即使在小的基因组区域，许多肿瘤抑制基因（TSG）也彼此相邻。它们可能以不同的作用参与不同类型的肿瘤，并且可能受到不同人群的遗传背景以及环境污染物（吸烟、职业暴露）的影响。本综述将讨论基因组缺失的分子分析方法，以揭示3p21处的致癌基因，总结关于该区域肿瘤抑制基因的现有知识，并描述上皮癌发病机制的一种可能模型。
