Next Generation Sequencing of Genes With Epigenetic Alterations in Mastocytosis

Mastocytosis is a neoplastic disease of the bone marrow associated with the risk of frequent and severe allergic reactions. However, the genetic predisposition is not fully understood, and the crucial element in pathogenesis is the presence of the oncogenic KIT p. D816 V gene mutation. The epigenetic mechanism has also been suggested as playing a role in mastocytosis.

Based on our previous epigenetic studies, we have selected 110 candidate genes which were sequenced by next generation sequencing (NGS) to identify somatic mutations.

The study group consisted of 32 patients with mastocytosis (16 females and 16 males) plus 16 controls (8 females and 8 males). Whole peripheral blood was collected from all the subjects and genotyped by NGS on the Illumina platform (targeted sequencing).

We analysed 4272 genetic variations in the pre-selected candidate genes and found five regions that showed a significant difference between the patient and control group. Two of them were found in the TET2 gene located on chromosome 4 and the other three alterations were found in the genes DNMT3A, SETD2 and BRD4 located on chromosomes 2, 3 and 19, respectively. Two out of the five genetic variants have not been previously reported, despite the fact that all four genes have been described to be associated with mastocytosis.

The results align with our previous findings, which determined TET2, DNMT3A, SETD2 and BRD4 genes as promising candidates for further analysis, warranting future study in a larger cohort of mastocytosis patients.