Lairmore T C, Norton J A
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Surg. 1997 Jan;173(1):37-41; discussion 42-3. doi: 10.1016/S0002-9610(96)00363-7.
The three known mechanisms of cellular transformation and oncogenesis include mutations in proto-oncogenes, inactivation of both copies of a tumor suppressor gene, and defects in DNA mismatch repair genes. Examples of each are included to substantiate the importance of understanding these mechanisms. RET is a proto-oncogene that is fundamental to the pathogenesis, and in the current era, molecular diagnosis of MEN 2 syndromes. TP53 is a tumor suppressor gene that is mutated in individuals with Li-Fraumeni syndrome. CDKN2 is a tumor suppressor gene that is mutated in pancreatic cancers and is associated with a poorer prognosis and the development of melanoma. MSH2 is a mismatch repair gene that is important in the pathogenesis of HNPCC and Muir-Torre syndrome. Altered gene function such as loss of DCC in colon cancers may affect cell adhesion properties and promote metastases. As we begin to better define and understand the mechanisms of neoplasia, we will be able to improve current diagnosis and treatment.
细胞转化和肿瘤发生的三种已知机制包括原癌基因突变、肿瘤抑制基因的两个拷贝均失活以及DNA错配修复基因缺陷。每种机制都列举了实例以证实理解这些机制的重要性。RET是一种原癌基因，对发病机制以及当前时代MEN 2综合征的分子诊断至关重要。TP53是一种肿瘤抑制基因，在李-弗劳梅尼综合征患者中发生突变。CDKN2是一种肿瘤抑制基因，在胰腺癌中发生突变，与较差的预后和黑色素瘤的发生有关。MSH2是一种错配修复基因，在HNPCC和穆尔-托里综合征的发病机制中起重要作用。结肠癌中DCC等基因功能改变可能影响细胞黏附特性并促进转移。随着我们开始更好地界定和理解肿瘤形成机制，我们将能够改进当前的诊断和治疗方法。
