TITLE:
RASSF1A Methylation Status and BRAF V600E Immunohistochemical Expression in Odontogenic Lesions
AUTHORS:
Chatchaphan Udompatanakorn, Naomi Yada, Kou Matsuo
KEYWORDS:
Odontogenic Lesions, DNA Methylation, RASSF1A, Immunohistochemistry, BRAF V600E
JOURNAL NAME:
Open Journal of Pathology,
Vol.10 No.3,
June
19,
2020
ABSTRACT: Background: The etiology and pathogenesis of odontogenic lesions remain to be determined. Previous studies have identified epigenetic and genetic alterations that may be relevant to lesions progression and development. Hypermethylation of the Ras association domain family protein 1A (RASSF1A) has been observed in a variety of human cancers. However, the methylation status of RASSF1A in odontogenic lesions remains unknown. Thus, the aim of this study was to investigate the prevalence of RASSFA promoter hypermethylation and v-raf murine sarcoma viral oncogene homolog B V600E mutant (BRAF V600E) expression as well as the correlations between these alterations and clinicopathological features of patients with odontogenic lesions. Methods: We subjected 66 formalin-fixed, paraffin-embedded odontogenic lesions [ameloblastoma (AM), 21; ameloblastic carcinoma (AC), 6; odontogenic keratocyst (OKC), 19; and dentigerous cyst (DC), 20] to methylation-specific polymerase chain reaction to determine RASSF1A hypermethylation and immunohistochemistry to detect BRAF V600E protein expression. Results: We observed RASSF1A hypermethylation in 20% (4/20; methylation could not be detected in one lesion), 100% (6/6), 26.3% (5/19), and 5% (1/20) of AM, AC, OKC, and DC samples, respectively. RASSF1A methylation was significantly more frequently observed in AC relative to AM, OKC, and DC (p Conclusions: Concomitant RASSF1A methylation and positive BRAF V600E expression are commonly observed in AC, which may contribute to AC tumorigenesis.