Mutations of K-ras oncogene in human adrenal tumours in Taiwan

Abstract

Recently, we have found a high frequency of p53 gene mutations in human functional adrenal tumours. As the tumorigenesis is a multigene defect, we believe that other oncogenes may also be involved in the initiation or progression of adrenal tumours. Using the single-strand conformational polymorphism (SSCP) method, we chose the ras oncogenes as the target in this screening procedure because their high mutation rates were detected in thyroid tumours. For the ras oncogenes analysed, exon 1 to exon 2 of H-ras and K-ras genes in the tumour tissues of 13 Conn's syndrome, two adrenal Cushing's syndrome, two non-functional adrenal tumours, one adrenocortical hyperplasia and eight phaeochromocytomas and its paired adjacent normal adrenal tissues were amplified and sequenced. No mutations were detected in the H-ras gene. But mutations of the K-ras gene were detected in 46% (6 of 13) of Conn's syndrome; the hot spots were located at codon 15, 16, 18 and 31, which were different from those previously found in other tumours (codon 12, 13 and 61). Northern blot analysis with 1.1 kb K-ras cDNA revealed that K-ras mRNA was more than tenfold over-expressed in four of Conn's syndrome, one case of Cushing's syndrome and one case of adrenocortical hyperplasia. The mutation sites and mutation type were not found in other tissues, which conferred that this was highly related to adrenocortical tumours. Yet, the correlation between K-ras oncogene and adrenocortical tumours needs to be clarified by further studies.