title: Defects of the Carney complex gene (PRKAR1A) in odontogenic tumors.
abstract: The surgical treatment of some odontogenic tumors often leads to tooth and maxillary bone loss as well as to facial deformity. Therefore, the identification of genes involved in the pathogenesis of odontogenic tumors may result in alternative molecular therapies. The PRKAR1A gene displays a loss of protein expression as well as somatic mutations in odontogenic myxomas, an odontogenic ectomesenchymal neoplasm. We used a combination of quantitative RT-PCR (qRT-PCR), immunohistochemistry, loss of heterozygosity (LOH) analysis, and direct sequencing of all PRKAR1A exons to assess if this gene is altered in mixed odontogenic tumors. Thirteen tumors were included in the study: six ameloblastic fibromas, four ameloblastic fibro-odontomas, one ameloblastic fibrodentinoma, and two ameloblastic fibrosarcomas. The epithelial components of the tumors were separated from the mesenchymal by laser microdissection in most of the cases. We also searched for odontogenic pathology in Prkar1a(+) (/) (-) mice. PRKAR1A mRNA/protein expression was decreased in the benign mixed odontogenic tumors in association with LOH at markers around the PRKAR1A gene. We also detected a missense and two synonymous mutations along with two 5'-UTR and four intronic mutations in mixed odontogenic tumors. Prkar1a(+) (/) (-) mice did not show evidence of odontogenic tumor formation, which indicates that additional genes may be involved in the pathogenesis of such tumors, at least in rodents. We conclude that the PRKAR1A gene and its locus are altered in mixed odontogenic tumors. PRKAR1A expression is decreased in a subset of tumors but not in all, and Prkar1a(+) (/) (-) mice do not show abnormalities, which indicates that additional genes play a role in this tumor's pathogenesis.
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Sílvia F
authors: SF
authors: Sousa
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Ricardo S
authors: RS
authors: Gomez
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Marina G
authors: MG
authors: Diniz
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Vanessa F
authors: VF
authors: Bernardes
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Flávia F C
authors: FF
authors: Soares
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: João Artur R
authors: JA
authors: Brito
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Sophie
authors: S
authors: Liu
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Hélder Antônio R
authors: HA
authors: Pontes
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil.
authors: Constantine A
authors: CA
authors: Stratakis
authors: Department of Oral Surgery and PathologySchool of DentistryDepartment of PathologyBiological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, 6627, Belo Horizonte, Minas Gerais CEP 31270-901, BrazilSection on Endocrinology and GeneticsProgram on Developmental Endocrinology and Genetics (PDEGEN), NIH, Bethesda, Maryland, USAJoão de Barros Barreto University HospitalUniversidade Federal do Pará (UFPA), Belém, Brazil carolinacgomes@ufmg.br.
authors: Carolina C
authors: CC
authors: Gomes
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D056733:Carney Complex / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002648:Child; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009808:Odontogenic Tumors / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009810:Odontoma / Q000473:pathology*; D055815:Young Adult
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; C517835:Prkar1a protein, mouse
keywords: ameloblastic fibro-odontoma; ameloblastic fibrodentinoma; ameloblastic fibroma; ameloblastic fibrosarcoma; benign tumors; loss of heterozygosity; mixed odontogenic tumors