말단비대증 환자의 뇌하수체 종양조직에서 H - ras 유전자 변이의 가능성 = A Study about the Involvement of H - ras Oncogene in Acromegalic Patients

다국어 초록 (Multilingual Abstract)

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다국어 초록 (Multilingual Abstract)

Backround: Little is known about the mechanism of tumorigenesis in pituitary adenomas. An important finding in somatotroph adenomas is that a somatic mutation may convert a G protein, Gs(α) into a putative oncogene termed gsp via point mutations at two critcal sites. The ras protooncogenes are structurally related to the G-protein family and are involved in cell proliferation and differentiation. Although ras oncogene mutations have been indentified in a wide variety of human neoplasm, only one case was reported as containting single point mutation in a patient with invasive prolactinoma, In this report we used oligonucleotide-specific hybridization to screen ras mutations in 13 acromegalic tumors. Methods: Pituitary tissue samples were derived from a central portion of the paraffin embedded pituitary tumor to minimize the possibility of contamination with normal tissue. Genomic DNA was isolated and purified from tumor tissue and amplified by the standard PCR method. Amplified DNAs from each of the region of H-ras genes (12/13 and 61) were analyzed for potential ras mutations using oligonucleotide-specific hybridization as described previously. Results: Wild type radiolabelled oligoncleotides were hybridized to the amplified DNAs from the patients' tumor and to the positive specimens. They were, however, easily striped out at 68℃ by nonstringent washing procedures except control (wild type) specimens. All radiolabelled mutant oligonucleotides could be easily striped out of 13 specimens except a control mutant specimen by the same procedure. Conclusion: We could not find any H-ras mutation that might not be frequently found in acromegalic patients, and that gsp (Gsa mutation) or mutations in the PKA system-related proteins might be the main oncogene in acromegalic patients. However further efforts to find the other somatic mutations including K-ras and N-ras should be given to these patients for more precise understanding of pathogenesis and for planning of the better treatment.