The landscape of genetic alterations in ameloblastomas relates to clinical features

Gültekin, Sibel Elif; Aziz, Reem; Heydt, Carina; Şengüven, Burcu; Zöller, Joachim E.; Safi, Ali Farid; Kreppel, Matthias; Buettner, Reinhard

doi:10.1007/s00428-018-2305-5

Cited by 58 publications

(117 citation statements)

References 18 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…One possible explanation for this relatively high prevalence of BRAF V600E mutations is racial and genetic differences. In a study of genetic alterations in ameloblastoma, multiple gene mutations are more frequently found in German and French patients than Turkish ones, suggesting that genetic background may influence mutational spectra . Moreover, conflicting results regarding BRAF V600E frequency have been presented in odontogenic keratocyst (OKC).…”

Section: Discussionmentioning

confidence: 99%

“…Second, other EMT‐TFs such as ZEB families are involved in tumorigenesis of ameloblastoma in association with BRAF V600E. Last, material types may affect the results of correlation analysis, considering that contrasting conclusions about the relationship between BRAF V600E and EMT have been drawn in melanoma and PTC depending on whether cell lines or tissue samples were used . Further investigations are needed to test these hypotheses and to clarify the biological role of BRAF V600E and EMT in ameloblastoma and other tumors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial‐mesenchymal transition

Cho

Yoon

et al. 2019

J Oral Pathology Medicine

View full text Add to dashboard Cite

Background BRAF V600E mutations are activating mutations that have recently been detected in ameloblastoma. However, their prevalence has not been reported in East Asian patients with ameloblastoma and their clinicopathological significance remains unclear. In this study, we examined the prevalence and clinicopathological significance of BRAF V600E mutations in Korean patients with ameloblastoma. In addition, we investigated the relationship between BRAF V600E mutations and epithelial‐mesenchymal transition, which has not been studied in ameloblastoma. Methods Thirty ameloblastoma tissue samples were collected, and DNA isolation, polymerase chain reaction, and Sanger sequencing were performed to detect BRAF V600E mutations. Immunohistochemistry was carried out using antibodies against two epithelial‐mesenchymal transition‐inducing transcription factors, Twist and Snail. Associations of BRAF V600E mutations with clinicopathological factors and expression of Twist and Snail were statistically analyzed. Results We found a high frequency (90.0%) of BRAF V600E mutations, and mutation status was not associated with clinicopathological factors including age, tumor location, and recurrence. Positive expression of Twist and Snail was observed in 33.3% and 56.7% of cases, respectively, and associated with recurrence (P = 0.020 and 0.010, respectively). There was no correlation between BRAF V600E mutation status and expression of Twist and Snail (P = 1.000, for both). Conclusions A higher prevalence of BRAF V600E mutations was identified in Korean patients with ameloblastoma compared with previous studies, which indicates that BRAF‐targeted therapies can be widely used for refractory ameloblastomas. Furthermore, our findings suggest that BRAF V600E mutations and epithelial‐mesenchymal transition may act independently in the development of ameloblastoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial‐mesenchymal transition

Cho

Yoon

et al. 2019

J Oral Pathology Medicine

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…Advanced next generation sequencing (NGS) analyses identified the high frequency of BRAF V600E and SMO L412F mutations in ameloblastoma . In 2018, Gültekin et al reported novel somatic mutation of oncogenes and tumor suppressor genes in addition to BRAF and SMO mutations . Using cell culture model with established ameloblastoma cell lines, Nakao et al reported that fibroblast growth factor (FGF) −7 and −10 stimulates ameloblastoma proliferation .…”

Section: Introductionmentioning

confidence: 99%

Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma

et al. 2020

View full text Add to dashboard Cite

Ameloblastoma is a rare odontogenic benign tumor accounting for less than 1% of head and neck tumors. Advanced next generation sequencing (NGS) analyses identified high frequency of BRAF V600E and SMO L412F mutations in ameloblastoma.Despite the existence of whole genomic sequence information from patients with ameloblastoma, entire molecular signature of and the characteristics of ameloblastoma cells are still obscure. In this study, we sought to uncover the molecular basis of ameloblastoma and to determine the cellular phenotype of ameloblastoma cells with BRAF mutations. Our comparative cDNA microarray analysis and gene set enrichment analysis (GSEA) showed that ameloblastoma exhibited a distinct gene expression pattern from the normal tissues: KRAS-responsive gene set is significantly activated in ameloblastoma. Importantly, insulin like growth factor 2 (IGF2), a member of KRAS-responsive genes, enhances the proliferation of an ameloblastoma cell line AMU-AM1 with BRAF mutation. In addition, Toll-like receptor 2 (TLR2) knockdown readily inactivated KRAS-responsive gene sets as well as increases caspase activities, suggesting that TLR2 signaling may mediate cell survival signaling in ameloblastoma cells. Collectively, the findings may help to further clarify the pathophysiology of ameloblastoma and lead to the development of precision medicine for patients with ameloblastoma.

show abstract

“…It is suggested that 46% to 82% of solid/multicystic ameloblastomas harbors BRAF V600E mutation (Brown et al, ; Guan et al, ; Kurppa et al, ; Sweeney et al, ), while UAM demonstrated higher BRAF V600E mutation frequency (63%–94%) (Heikinheimo et al, ; Pereira et al, ). More recent studies revealed that less common cell types of ameloblastoma showed different rates of BRAF V600E mutation: acanthomatous (44%, 7/16), granular (50%, 2/4), and basaloid (33%, 2/6) (Gultekin et al, ; You et al, ). However, ameloblastoma with mucous cell differentiation still has no particular BRAF V600E up to date mutation data.…”

Section: Introductionmentioning

confidence: 99%

Ameloblastoma with mucous cells: A clinicopathological, BRAF mutation, and MAML2 rearrangement study

et al. 2020

View full text Add to dashboard Cite

Objectives To investigate the clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement of ameloblastoma with mucous cell differentiation. Materials and Methods Five cases of ameloblastoma with mucous cell differentiation were retrospectively studied. Clinicopathological features, BRAF V600E mutation, and MAML2 rearrangement were analyzed. Follow‐up information was available for all cases. Results Of five cases, two cases were male and three were female, aged 18–55 years. Four cases were located in the mandible and one case in the maxilla. Histologically, four of the five cases (80%) presented with cystic features and three of the five cases (60%) with varying degrees of squamous metaplasia. The mucous cells were located in the epithelial islands or the luminal aspect of the cystic cavities. The BRAF V600E mutation was found in three of five cases (60%). All the cases showed no MAML2 rearrangement. Two cases were recurrent lesions, and one case had a local recurrence during the follow‐up. Conclusions Ameloblastoma with mucous cell differentiation is closely related to the cystic features, squamous metaplasia, and shows a high prevalence of BRAF V600E mutation. The absence of MAML2 rearrangement reveals that ameloblastoma with mucous cell differentiation and central mucoepidermoid carcinoma (MEC) are two distinct tumor entities.

show abstract

The landscape of genetic alterations in ameloblastomas relates to clinical features

Cited by 58 publications

References 18 publications

High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial‐mesenchymal transition

High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial‐mesenchymal transition

Discovery of novel molecular characteristics and cellular biological properties in ameloblastoma

Ameloblastoma with mucous cells: A clinicopathological, BRAF mutation, and MAML2 rearrangement study

Contact Info

Product

Resources

About