Scully C, Field J K, Tanzawa H
Eastman Dental Institute for Oral Health Care Sciences, University College London, University of London, 256 Gray's Inn Road, WC1X 8LD, London, UK.
Oral Oncol. 2000 Jul;36(4):311-27. doi: 10.1016/s1368-8375(00)00021-x.
Carcinogenesis is the result of a series of genetic mutations resulting in unregulated growth of a clone of cells and the development of malignant lesion that is largely monoclonal though, with the evolution of further genetic changes, there develops a degree of heterogeneity in the tumour. DNA technology, especially allelic imbalance (loss of heterozygosity) studies have identified chromosomal changes in oral carcinoma and head and neck squamous cell carcinoma (SCCHN), suggestive of the involvement of tumour suppressor genes (TSGs), particularly in chromosomes 3, 9, 11 and 17. The regions most commonly identified have included 3p, especially 3p14.2 (FHIT); 3p24, and 3p21.3, where the TSGs involved are as yet unidentified; 9p21 where p16 (INK4A/MTS-1] is the main target TSG; and 17p13 where p53 is the major target TSG. Over-expression of oncogenes, genes mainly involved in cell signalling, especially those on chromosome 11 (PRAD-1 in particular) and 17 (H-ras) and mutations in DNA repair genes, have also been implicated in the carcinogenesis of SCCHN.
致癌作用是一系列基因突变的结果，这些突变导致细胞克隆的生长失控以及恶性病变的发展。虽然肿瘤在很大程度上是单克隆性的，但随着进一步基因变化的演变，肿瘤会出现一定程度的异质性。DNA技术，尤其是等位基因失衡（杂合性缺失）研究，已确定口腔癌和头颈部鳞状细胞癌（SCCHN）中的染色体变化，提示肿瘤抑制基因（TSG）参与其中，特别是在3号、9号、11号和17号染色体上。最常确定的区域包括3p，尤其是3p14.2（FHIT）；3p24和3p21.3，其中涉及的TSG尚未确定；9p21，其中p16（INK4A/MTS-1）是主要的靶标TSG；以及17p13，其中p53是主要的靶标TSG。癌基因的过度表达，主要参与细胞信号传导的基因，特别是11号染色体（尤其是PRAD-1）和17号染色体（H-ras）上的基因，以及DNA修复基因的突变，也与SCCHN的致癌作用有关。
