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Infrequent mutations of p16INK4A and p15INK4B genes in human pituitary adenomas
K Yoshimoto1, C Tanaka, S Yamada
1Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima, Kuramoto-cho, Japan.
Abstract:
The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively. Mutations and deletions of the p16INK4A gene have been found in melanomas and many other types of tumors. To assess the role of the p16INK4A and p15NK4B 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 p161NK4A and p15INK4B genes. To identify pituitary adenomas which had lost 9p21-22, pituitary adenomas were genotyped with markers flanking the p16INK4A and p15INK4B loci. The frequency of mutations in coding regions of the p16INK4A and the p15INK4B 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 p16INK4A and p15INK4B genes are not required for tumorigenesis of the pituitary gland.
Insights
Mutations in the p16INK4A and p15INK4B genes are not essential for pituitary gland tumor development. This study found no tumor-specific mutations in these genes in pituitary adenomas, suggesting other mechanisms drive tumorigenesis.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- The p16INK4A and p15INK4B genes are tumor suppressors located at chromosome 9p21.
- Alterations in p16INK4A are implicated in various cancers, including melanoma.
- Their role in pituitary gland tumorigenesis remains to be fully elucidated.
Purpose of the Study:
- To investigate the involvement of p16INK4A and p15INK4B genes in pituitary adenoma development.
- To determine if mutations or loss of heterozygosity in these genes contribute to pituitary tumorigenesis.
Main Methods:
- Analysis of 33 pituitary adenomas (31 sporadic, 2 familial acromegaly) for genetic alterations.
- Genotyping using markers flanking the p16INK4A and p15INK4B loci to detect loss of heterozygosity (LOH) on 9p21-22.
- Screening for mutations in the coding regions of p16INK4A and p15INK4B using PCR-SSCP and sequencing.
Main Results:
- Two out of 33 pituitary adenomas exhibited loss of 9p21-22 sequences.
- No tumor-specific mutations in the p16INK4A or p15INK4B genes were identified in any of the analyzed pituitary adenomas.
- The observed LOH in two cases did not correlate with specific mutations.
Conclusions:
- Mutations in the p16INK4A and p15INK4B genes are not a prerequisite for the development of pituitary adenomas.
- These genes do not appear to be major drivers of tumorigenesis in the pituitary gland.
- Further research is needed to identify the genetic factors involved in pituitary tumor formation.