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

The Hamon Center for Therapeutic Oncology Research, and, Department of Pathology, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235
^a Author for correspondence. Fax 214 648-4924; e-mail gazdar@simmons.swmed.edu.

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

Although about 20–25% of human tumors have ras mutations, especially involving the K-ras gene, the distribution demonstrates considerable tumor type specificity (4)(5). Thus, although K-ras mutations are found in nearly 90% of pancreatic carcinomas and about 50% of colorectal carcinomas, they are rare in breast cancers. Lung . . . [Full Text of this Article]

References

The following articles in journals at HighWire Press have cited this article:

				S. J. Clayton, F. M. Scott, J. Walker, K. Callaghan, K. Haque, T. Liloglou, G. Xinarianos, S. Shawcross, P. Ceuppens, J. K. Field, et al. K-ras Point Mutation Detection in Lung Cancer: Comparison of Two Approaches to Somatic Mutation Detection Using ARMS Allele-specific Amplification Clin. Chem., December 1, 2000; 46(12): 1929 - 1938. [Abstract] [Full Text] [PDF]