title: Tumor suppressor gene ZAC/PLAGL1: altered expression and loss of the nonimprinted allele in pheochromocytomas.
abstract: ZAC/PLAGL1 is a novel imprinted tumor suppressor gene encoding an important inducer of cell cycle arrest and apoptosis, and found to be lost during tumorigenesis. We analyzed the significance of ZAC in the development of a rare, usually benign tumor of the adrenal gland: pheochromocytoma (PCC). Twenty-four PCCs were analyzed for the loss of the active nonimprinted allele of ZAC, and nine of the twenty-four PCCs were also assayed for expression of the protein. In thirteen of the cases, a paired nonmalignant tissue was available for analysis. Methylation-specific polymerase chain reaction revealed frequent (15 of 23, 65%) loss of unmethylated DNA in the imprinting control region of ZAC. Immunohistochemistry identified reduced ZAC expression in 56% (5 of 9) of the subset cases. Four of the five PCC cases where reduced expression of ZAC was observed were also positive for the loss of the active ZAC allele. Additionally, the loss of ZAC expression was also found to be frequent in a series of capillary hemangioblastomas and gliomas (6 of 6, 100%, and 17 of 27, 63%, respectively) examined for comparison. In conclusion, our study suggests the involvement of the imprinted ZAC gene in the pathogenesis of PCC.
authors.affiliation: Vilnius University, Lithuania. sonata.jarmalaite@gf.vu.lt
authors.forename: Sonata
authors.initials: S
authors.lastname: Jarmalaite
authors.forename: Aida
authors.initials: A
authors.lastname: Laurinaviciene
authors.forename: Justina
authors.initials: J
authors.lastname: Tverkuviene
authors.forename: Neringa
authors.initials: N
authors.lastname: Kalinauskaite
authors.forename: Donatas
authors.initials: D
authors.lastname: Petroska
authors.forename: Tom
authors.initials: T
authors.lastname: Böhling
authors.forename: Kirsti
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D016543:Central Nervous System Neoplasms / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D018392:Genomic Imprinting; D018325:Hemangioblastoma / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins