Sensitive Methods for the Detection of ras Mutations in Lung Cancer: Some Answers, More Questions

作者: Adi F Gazdar , Arvind Virmani

DOI: 10.1093/CLINCHEM/44.7.1376

关键词: G proteinBiologyLipid modificationPoint mutationMutationOncogeneGTPaseMolecular biologyCancer researchSignal transductionHRAS

摘要: The ras family consists of three evolutionarily conserved genes, H- , N- and K- . genes code for 21-kDa proteins that mediate signal transduction between cell surface receptors intracellular regulatory molecules. attach to the inner cytoplasmic membrane via a posttranslationally added farnesyl group. This lipid modification is essential function, considerable recent interest has focused on agents inhibit enzyme responsible, transferase, as mechanism block growth tumors having mutations (1). Ras homologous larger “G proteins” exist in two states, GDP- GTP-bound. Only GTP-bound form effective at mediating response, there dynamic interconversion forms. Point are most frequent dominant oncogene mutation found human usually target only codons: 12, 13, 61. Most activating defective GTPase activity thus locked into form, resulting continuous stimulation. Detection enables us understand cancer biology pathogenesis may be clinical importance by providing information useful early diagnosis prognosis development novel therapeutic approaches (1)(2). As discussed below, detected large variety methodologies, both conventional and, reported this issue Clinical Chemistry supersensitive (3). Although about 20–25% have mutations, especially involving gene, distribution demonstrates tumor type specificity (4)(5). Thus, although nearly 90% pancreatic carcinomas 50% colorectal carcinomas, they rare breast cancers. Lung cancers an example heterogeneity …

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