Promoter CpG methylation of multiple genes in pituitary adenomas: frequent involvement of caspase-8

M. Bello, Jose De Campos, Alberto Isla, Cacilda Casartelli, Juan Rey
2006 Oncology Reports  
The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14 ARF , p16 INK4a , p73, MGMT, DAPK, in a series of 35 tumours using methylationspecific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of
more » ... se genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14 ARF , 34% for p16 INK4a , 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.
doi:10.3892/or.15.2.443 fatcat:rahcqd75kjdblk46665ixcq63q