Infrequent mutations of p16(INK4A) and p15(INK4B) genes in human pituitary adenomas

The p16(INK4A) and p15(INK4B) genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively, Mutations and deletions of the p16(INK4A) gene have been found in melanomas and many other types of tumors. To assess the role of the p16(INK4A) and p15(INK4B) genes in tumorigenesis of the pituitary gland, 31 sporadic pituitary adenomas and 2 pituitary adenomas in familial acrogigantism were examined for loss of heterozygosity on 9p21-22 and screened for mutations in the p16(INK4A) and p15(INK4B) genes. To identify pituitary adenomas which had lost 9p21-22, pituitary adenomas were genotyped with markers flanking the p16(INK4A) and p15(INK4B) loci. The frequency of mutations in coding regions of the p16(INK4A) and the p15(INK4B) genes in pituitary adenomas was determined with polymerase chain reaction-single strand conformation polymorphism analysis and sequencing of variants, Of the 33 pituitary adenomas, two revealed loss of 9p21-22 sequences, but none of them had tumor-specific mutations, We conclude that mutations of the p16(INK4A) and p15(INK4B) genes are not required for tumorigenesis of the pituitary gland.