Endocrine Abstracts

Context: Pituitary tumorigenesis does not fit into the most common model of cancer development driven by gene mutations. Instead, epigenetic mechanisms have been widely involved. Among them, aberrant DNA methylation at CpG sites is one of epigenetic hallmarks of tumour cells. There are several methods to study the epigenetic regulation of genome activity, from DNA methylation arrays to more specific DNA methylation analysis such as pyrosequencing, Methylation-Specific PCR (MS-PCR) or MS-multiplex ligation-dependent probe amplification (MS-MLPA) of selected genes.

M & M: We studied the DNA-promoter methylation and gene expression of 35 tumour suppressor genes in 105 pituitary neuroendocrine tumors (PitNETs) by MS-MLPA and quantitative real-time PCR techniques, looking for differences among subtypes and between functional and invasive behaviour of tumors. Moreover, I revised the most relevant results published in the literature.

Results: We observed different methylation patterns among PitNET subtypes. The methylation status correlated negatively with its gene expression in some but not all methylated genes. Moreover, some genes appeared more frequently methylated in macro and invasive tumours than in micro or non-invasive ones. Finally, we found significant differences between functioning and non-functioning corticotroph tumours. The revision of the literature showed contradictory results related to invasion and functionality, mainly due to the sample studied and the techniques used.

Conclusions: It seems clear that aberrant DNA methylation of several genes play an important role in the behaviour of PitNETs. However, as pituitary tumours come from different cell lineages which can show different patterns of methylation, it is necessary to consider the pituitary subtypes as different entities.