PTCH1 isoforms in odontogenic keratocysts.
Odontogenic keratocyst (OKC) is an aggressive benign odontogenic neoplasm associated with PTCH1 alteration. PTCH1 has several isoforms generated by use of different first exon (1b, 1d and 1e). These isoforms code for proteins with different functions, expression profiles and transcriptional regulation. The aim of the present study was to investigate the expression of PTCH1 first exons in OKC tumors to shed light on scenery whereby PTCH1 coordinates OKC tumorigenesis. Forty OKC, including 12 sporadic and 28 associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS), were included in the study. The variants 1b, 1d and 1e were investigated by RT-PCR. The exon 1b was detected in 90% of OKC and none of the dental follicle (control). Most of the OKC, sporadic and syndromic, and all of the samples of dental follicles demonstrated the expression of 1d mRNA. All primary OKC had 1b mRNA while 4 (24%) lesions marsupialized lost 1b expression. In addition, the pattern of exon 1 expression observed in oral mucosa adjacent to the OKC was similar to the OKC tumor. In conclusion, this report showed overactivity of Hedgehog (HH) pathway in OKC lesion and at adjacent oral mucosa. We also demonstrated that marsupialization could alter PTCH1 variants profiling in some OKC cases.
Diniz
Marina Gonçalves
MG
Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
Borges
Erica Rievrs
ER
Guimarães
André Luiz Sena
AL
Moreira
Paula Rocha
PR
Brito
João Artur Ricieri
JA
Gomez
Marcus Vinícius
MV
De Marco
Luiz
L
Gomez
Ricardo Santiago
RS
D000293:Adolescent; D000328:Adult; D001478:Basal Cell Nevus Syndrome / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism; D009807:Odontogenic Cysts / Q000235:genetics / Q000378:metabolism*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D055815:Young Adult
C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020033:Protein Isoforms; D011956:Receptors, Cell Surface