Advances in molecular genetics.
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.
Lairmore
T C
TC
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Norton
J A
JA
D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy; D015179:Colorectal Neoplasms / Q000235:genetics / Q000628:therapy; D005260:Female; D005544:Forecasting; D013502:General Surgery / Q000639:trends*; D006801:Humans; D008495:Medical Oncology / Q000639:trends*; D008967:Molecular Biology / Q000639:trends*; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000628:therapy; D000090063:Proto-Oncogene Mas; D014481:United States