title: Models of parent-of-origin tumorigenesis in hereditary paraganglioma.
abstract: Paraganglioma and pheochromocytoma are neuroendocrine tumors that originate from either the sympathetic or the parasympathetic branches of the autonomic nervous system. Although 14 different genes have been linked to paraganglioma/pheochromocytoma, a subgroup of these genes is associated with hereditary paraganglioma-pheochromocytoma, the genes related to mitochondrial succinate dehydrogenase (SDH) including SDHA, SDHB, SDHC, SDHD and the assembly factor SDHAF2. Unlike mutations in other SDH subunit genes, mutations in SDHD and SDHAF2 show a remarkable parent-of-origin dependent tumorigenesis in which tumor formation almost exclusively occurs following paternal transmission of the mutation. To date, three different models have sought to explain the striking inheritance pattern seen in SDHD and SDHAF2-linked families. Despite the fact that the models suffer to varying degrees from a lack of experimental verification, all three models have made some attempt to incorporate current data and understanding of this phenomenon. In this review, we discuss our present understanding of this phenomenon and describe the three models that seek to explain the inheritance pattern in SDHD and SDHAF2-linked families.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Attje S
authors.initials: AS
authors.lastname: Hoekstra
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: j.p.l.bayley@lumc.nl.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bayley
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C079439:MXD1 protein, human; D046912:Multiprotein Complexes; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D013385:Succinate Dehydrogenase
keywords: MAX; Paraganglioma; Pheochromocytoma; SDHAF2; SDHD