Abstract
Endocrine tumors are neoplasms originating from specialized hormone-secreting cells. They can develop as sporadic tumors, caused by somatic mutations, or in the context of familial Mendelian inherited diseases. Congenital forms, manifesting as syndromic or non-syndromic diseases, are caused by germinal heterozygote autosomal dominant mutations in oncogenes or tumor suppressor genes. The genetic defect leads to a loss of cell growth control in target endocrine tissues and to tumor development. In addition to the classical cancer manifestations, some affected patients can manifest alterations of bone and mineral metabolism, presenting both as pathognomonic and/or non-specific skeletal clinical features, which can be either secondary complications of endocrine functioning primary tumors and/or a direct consequence of the gene mutation. Here, we specifically review the current knowledge on possible direct roles of the genes that cause inherited endocrine tumors in the regulation of bone modeling and remodeling by exploring functional in vitro and in vivo studies highlighting how some of these genes participate in the regulation of molecular pathways involved in bone and mineral metabolism homeostasis, and by describing the potential direct effects of gene mutations on the development of skeletal and mineral metabolism clinical features in patients.
Highlights
The specific clinical affections of bone tissue, and/or the deregulation of bone and mineral metabolism, leading to premature bone mass loss and osteoporosis, develop in a percentage of patients affected by inherited endocrine tumors, as primary manifestations of the syndrome and/or as a consequence of hormone-secreting neoplasms, being a cause of morbidity and disability
We reviewed the current knowledge, derived from in vitro and in vivo studies, about the possible role that some of the genes, whose germline mutations are responsible for inherited endocrine tumors, may have in the regulation of molecular pathways involved in skeletal development and bone and mineral metabolism homeostasis
We will discuss the ascertained molecular roles of the genes whose germline mutations are responsible for inherited endocrine tumors in the regulation of skeletal modeling and remodeling, and/or in the control of mineral metabolism homeostasis
Summary
The specific clinical affections of bone tissue, and/or the deregulation of bone and mineral metabolism, leading to premature bone mass loss and osteoporosis, develop in a percentage of patients affected by inherited endocrine tumors, as primary manifestations of the syndrome and/or as a consequence of hormone-secreting neoplasms, being a cause of morbidity and disability. The medical literature has poorly and marginally documented skeletal affections in inherited endocrine tumors, and a comprehensive and detailed review, focused on the roles of the genetic determinants of these diseases in the regulation of bone and mineral metabolism, and, possibly, in the development of skeletal manifestations, is missing. This review wants to offer clinicians an overview of the molecular mechanisms underlying bone and mineral metabolism alterations in different syndromic and non-syndromic inherited endocrine tumors, as possible bases for targeted clinical managements of skeletal pathological manifestations in these congenital diseases. We reviewed the current knowledge, derived from in vitro and in vivo studies, about the possible role that some of the genes, whose germline mutations are responsible for inherited endocrine tumors, may have in the regulation of molecular pathways involved in skeletal development and bone and mineral metabolism homeostasis
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