Oncogenes in human lung cancer.
The rapid pace of research in the genetics of human cancer will predictably render any review of the topic out of date by the time of its publication. Prospects for the near future will likely include the identification of a chromosome 3p gene(s) linked with the development of familial renal cancer and, perhaps, also lung cancer. In addition, the availability from the Human Genome Project of an increasing number of well-characterized markers will accelerate the search for additional human recessive oncogenes. Many questions still remain about the etiology of lung cancer and how to apply this information for patient care. For example, identification of the cell of origin for small cell and non-small cell lung cancers will facilitate our understanding of the development of these tumors and improve the possibilities for future preventive strategies. In addition, we now realize that these cancers arise from the sequential accumulation of multiple genetic mutations (Table 3; Fig. 1). Therefore, a central question is which of these targets are essential for the process of carcinogenesis, and whether there is a critical temporal order for this process with a defined premalignant phase in a discrete field of bronchial tissue. In addition, are there genetically inherited susceptibilities to the development of lung cancer (either directly or via variabilities in carcinogen metabolism) that could be accurately identified in the general population? Finally, is there a rate-limiting mutation and will the genetic correction of this defect suffice to restore growth regulation, or will the replacement of multiple gene products be required for tumor suppression? We are already witnessing the beginnings of the use of molecular diagnostic markers as a research tool for assigning prognostic information. The expression of neuroendocrine markers in non-small cell lung cancer has recently been applied as an indicator of the potential response to combination chemotherapy [15]. Similar methods are being applied to the expression of tumor suppressor genes or the presence of somatic mutations in dominant oncogenes such as the ras gene. However, the clinical benefit of this prognostic information with currently available treatment programs is still uncertain.(ABSTRACT TRUNCATED AT 400 WORDS)
R A
RA
Kratzke
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E
Shimizu
F J
FJ
Kaye
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D002893:Chromosomes, Human, Pair 3; D005799:Genes, Dominant; D005808:Genes, Recessive; D016161:Genes, Retinoblastoma; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009857:Oncogenes