Loss of heterozygosity of the PTCH gene in ameloblastoma

Farias, Lucyana Conceição; Gomes, Carolina Cavaliéri; Brito, João Artur Ricieri; Galvão, Clarice Ferreira; Diniz, Marina Gonçalves; Castro, Wagner Henriques; Bernardes, Vanessa Fátima; Marco, Luiz Armando De; Gomez, Ricardo Santiago

doi:10.1016/j.humpath.2011.08.026

Cited by 13 publications

(15 citation statements)

References 21 publications

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“…Previous investigations have assessed the molecular and genetic alterations related mainly to apoptosis, allelic loss of tumour suppressor genes, deregulation of the Sonic Hedgehog signalling pathway, and the clonality of these tumours [3,24,25]. …”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

et al. 2012

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BackgroundAn ameloblastoma is a benign odontogenic neoplasm with aggressive behaviour and high recurrence rates. The increased expression of matrix metalloproteinases (MMPs) has been reported in ameloblastomas. In the present study, we hypothesised that epigenetic alterations may regulate MMP expression in ameloblastomas.MethodsWe investigated the methylation status of the genes MMP-2 and MMP-9 in addition to mRNA transcription and protein expression in ameloblastomas. Methylation analysis was performed by both methylation-specific polymerase chain reaction (MSP-PCR) and restriction enzyme digestion to evaluate the methylation profile of MMP-2 and MMP-9 in 12 ameloblastoma samples and 12 healthy gingiva fragments, which were included as controls. Furthermore, we investigated the transcription levels of the genes by quantitative reverse-transcription PCR (qRT-PCR). Zymography was performed to verify protein expression in ameloblastomas.ResultsThe ameloblastomas showed a high frequency of unmethylated MMP-2 and MMP-9, whereas the healthy gingival samples presented a sharp prevalence of methylated MMPs. Higher expression levels of MMP-9 were found in ameloblastomas compared to healthy gingiva. However, no significant differences in the MMP-2 mRNA expression between groups was found. All ameloblastomas showed positive expression of MMP-2 and MMP-9 proteins.ConclusionsOur findings suggest that expression of MMP-9 is increased in ameloblastomas and is possibly modulated by unmethylation of the gene.

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Section: Discussionmentioning

confidence: 99%

Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

et al. 2012

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“…Amplification products were detected by capillary electrophoresis on an ABI PRISM 310 (Applied Biosystems, Foster City, CA). LOH was calculated as previously described by Farias et al ., 2012.…”

Section: Methodsmentioning

confidence: 99%

“…Genes involved in the odontogenesis process and tumor suppressor genes are the main targets of molecular studies of odontogenic tumors (Barreto et al ., 2000; Perdigão et al ., 2004; Gomes and Gomez, 2011; Farias et al ., 2012). In this context, our group described LOH (loss of heterozygosity) at tumor suppressor genes loci in the mixed odontogenic tumors AF and AFO, as well as in AFS (Galvão et al ., 2012).…”

Section: Introductionmentioning

confidence: 99%

Defects of the Carney complex gene (PRKAR1A) in odontogenic tumors

Sousa

Gomez

Diniz

et al. 2015

Endocrine-Related Cancer

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The surgical treatment of some odontogenic tumors often leads to tooth and maxillary bone loss as well as facial deformity. Therefore, the identification of genes involved in their pathogenesis may result in alternative molecular therapies. The PRKAR1A gene shows loss of protein expression, as well as somatic mutations in odontogenic myxomas, an odontogenic ectomesenchymal neoplasm. We used a combination of qRT-PCR, immunohistochemistry, LOH analysis and direct sequencing of all PRKAR1A exons to assess if this gene is altered in mixed odontogenic tumors. Thirteen tumors were included, being six ameloblastic fibromas, four ameloblastic fibro-odontomas, one ameloblastic fibrodentinoma and two ameloblastic fibrosarcomas. The epithelial component of the tumors was 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 PRKAR1A gene. We also detected a missense and two synonymous mutations, besides two 5’-UTR and four intronic mutations in the mixed odontogenic tumors. Prkar1a+/− mice did not show evidence of odontogenic tumor formation, suggesting that additional genes may be involved in their pathogenesis, at least in rodents. We conclude that the PRKAR1A gene and its locus are altered in mixed odontogenic tumors. PRKAR1A's expression is decreased in a subset of tumors but not in all, and Prkar1a+/− mice do not show abnormalities, suggesting that additional genes play a role in this tumor's pathogenesis.

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“…Markers and regions evaluated were as follows: P53 (17p13.1), AFM238WF2 (17p13.1), D9S162 (9p22-p13) D9S171 (9p22-p21), D9S157 (9p22), and D9S287 (9q22.3). Primers and PCR conditions used are described elsewhere [27,28]. The amplified PCR products were detected in 8 % polyacrylamide gel and were submitted to capillary electrophoresis on a ABI PRISM 310 sequencer (Applied Biosystems, Foster City, CA, USA), and data was analyzed using the Genescan software version 3.0 (Applied Biosystems, Foster City, CA, USA).…”

Section: Loss Of Heterozygosity Analysismentioning

confidence: 99%

Lip cancer and pre-cancerous lesions harbor TP53 mutations, exhibit allelic loss at 9p, 9q, and 17p, but no BRAFV600E mutations

et al. 2015

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Molecular mechanisms of lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) are unclear. We aimed at assessing loss of heterozygosity (LOH) and TP53 and BRAF V600E mutations in these lesions. Formalin-fixed paraffin-embedded (FFPE) samples of 17 LSCC and 16 AC were included, with additional 5 fresh LSCC genotyped for TP53 mutations. LOH was assessed by six polymorphic markers located at 9p22, 9q22, and 17p13 and correlated with cell proliferation (Ki-67) and P53 immunostaining. Direct sequencing of TP53 exons 2-11 (fresh samples), and exons 5-9 (FFPE samples) was carried out. BRAF V600E mutation was genotyped in eight LSCC. LOH occurred in at least one marker in 15/17 LSCC and in 9/16 AC. The marker exhibiting the highest frequency of allelic loss (FAL) in LSCC was D9S157 (8/12 informative cases) and D9S287 in AC (4/11 informative cases). Cell proliferation was not correlated with LOH or with the FAL and no correlation between P53 IHC and 17p LOH was observed. We found TP53 missense mutations in both lesions and nonsense in LSCC, including CC>TT transition, which is a marker of UV damage. BRAF V600E mutation was not detected. LOH and TP53 mutations detected in LSCC and AC may be associated with tumorigenesis, whereas BRAF V600E mutation does not seem to significantly contribute to LSCC pathogenesis.

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Loss of heterozygosity of the PTCH gene in ameloblastoma

Cited by 13 publications

References 21 publications

Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

Epigenetic regulation of matrix metalloproteinase expression in ameloblastoma

Defects of the Carney complex gene (PRKAR1A) in odontogenic tumors

Lip cancer and pre-cancerous lesions harbor TP53 mutations, exhibit allelic loss at 9p, 9q, and 17p, but no BRAFV600E mutations

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