Hemangioblastoma in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: a phenotypic overlap between VHL and HLRCC Syndromes

Abstract

Hemangioblastomas are rare vascularized central nervous system tumors, which can occur sporadically or be associated with von Hippel Lindau Syndrome. The pathogenesis of hemangioblastomas in von Hippel Lindau Syndrome is proposed to involve a pseudohypoxic intracellular state induced by dysregulation of hypoxia inducible factor alpha due to the absence of von Hippel Lindau protein complex mediated destruction. Dysregulation of fumarate hydratase, a tricarboxylic acid cycle enzyme, occurs in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome due to germline fumarate hydratase gene mutations, and also results in oncogenesis via hypoxia inducible factor alpha dysregulation. We present a case study of hemangioblastoma occurrence in a Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome patient and propose it as possible evidence of a phenotypic overlap between von Hippel Lindau and Hereditary Leiomyomatosis and Renal Cell Cancer Syndromes due to their overlapping role in the biochemical regulation of hypoxia inducible factor alpha.

Application Areas of Traditional Molecular Genetic Methods and NGS in relation to Hereditary Urological Cancer Diagnosis

“…been described. For example, a combination of type II papillary RCC and hemangioblastomas was observed in a patient with a 1.4 Mb deletion, which affected region 1q43, including nine genes in addition to FH [17]. It is worth noting that the role of germline FH mutations in carcinogenesis is not limited to HLRCC.…”