Open AccessRecurrent Alterations in the MAPK pathway in Sporadic Pyogenic Granuloma of Childhood
Author(s) -
Katharina Strobel,
Katja Maurus,
Henning Hamm,
Sabine Roth,
Matthias Goebeler,
Andreas Rosenwald,
Marion Wobser
Publication year - 2022
Publication title -
acta dermato-venereologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.982
H-Index - 83
eISSN - 1651-2057
pISSN - 0001-5555
DOI - 10.2340/actadv.v102.1119
Subject(s) - pyogenic granuloma , mapk/erk pathway , hras , protein kinase a , granuloma , cancer research , mitogen activated protein kinase , kinase , biology , medicine , mutation , gene , immunology , pathology , genetics , lesion , kras
Pyogenic granuloma is one of the most common vascular tumours. The cause of pyogenic granuloma was previously thought to be an inflammatory reaction with consecutive stimulation of endothelial cell proliferation. However, recent studies suggest that pyogenic granuloma may be driven by constitutive activation of the mitogen-activated protein kinase pathway. The aim of this study was to investigate the molecular profile of sporadic pyogenic granuloma of childhood, using a systematic approach scrutinizing potential aberrations within different oncogenic pathways. Within a retrospective setting pyogenic granuloma of 15 patients was analysed by targeted next generation sequencing using the Oncomine Focus Assay, which includes genes of key tumorigenic signalling pathways. Activating mutations were found in 4 out of 15 cases (27%). Two HRAS hotspot mutations (p.Gly13Arg, p.Ala59Thr), 1 BRAF (p.Val600Glu) mutation and a novel, previously not reported, MAP2K1 hotspot mutation (p.Glu203Lys) were identified. It is notable that all of these genes are involved in constitutive mitogen-activated protein kinase signalling. This study increases the range of underlying genetic alterations in pyogenic granuloma by identifying novel oncogenic mutations in crucial mitogen-activated protein kinase pathway genes. The results provide supporting evidence that activated mitogen-activated protein kinase signalling is a key driver in the pathogenesis of pyogenic granuloma, which might be exploited by targeted treatment approaches for selected cases.