Adenoid ameloblastoma harbors beta-catenin mutations

Bastos, Victor Coutinho; Coura, Bruna Pizziolo; Guimarães, Letícia Martins; Fernandes, Bianca Gomes; Chan, Alexander; Vargas, Pablo Agustı́n; Bastos‐Rodrigues, Luciana; Marco, Luiz Armando De; Hellstein, John W.; Thavaraj, Selvam; Wright, John M.; Odell, Edward; Gomez, Ricardo Santiago; Gomes, Carolina Cavaliéri

doi:10.1038/s41379-022-01125-4

Cited by 19 publications

(36 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11,13,30 Some odontogenic tumours have signature mutations, including BRAF p.V600E for ameloblastoma, KRAS p.G12V/R for AOT, and CTNNB1 mutations for ghost-cell-rich odontogenic lesions. 1,10,11,13,14,19,26 However, none of these mutations is diagnostic.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 Additionally, the identification of genetic mutations can raise possibilities of a relationship between entities, as for example the presence of CTNNB1 mutations in AA, odontogenic carcinoma with dentinoid, DGCT and other ghost cell-containing odontogenic tumours. 19 The identification of molecular alterations in odontogenic tumours can guide targeted therapies. Patients with aggressive and recurrent tumours might benefit from these therapies at least as a first step.…”

Section: Discussionmentioning

confidence: 99%

“…19 All, but one case, showed nuclear beta-catenin immunoexpression, indicating the pathway is activated even in the absence of the mutation. 19 Collectively, the molecular features of AA support its classification as a separate entity from ameloblastoma. However, there are cases for which the genetic basis remains unclear, and future work can better elucidate its relationship with DGCT and odontogenic carcinoma with dentinoid.…”

Section: Adenoid Ameloblastomamentioning

confidence: 96%

“…Considering that ghost cells may be present in AA and that CTNNB1 mutations are reported in ghost‐cell‐rich tumours, we further assessed CTNNB1 exon 3 mutations in AA and detected them in 44% (4/9) of cases (Figure 1). 19 All, but one case, showed nuclear beta‐catenin immunoexpression, indicating the pathway is activated even in the absence of the mutation 19 …”

Section: Benign Epithelial Odontogenic Tumoursmentioning

confidence: 99%

“…CTNNB1 mutations have been reported in DGCT, 16,26 pointing to shared genetic background with other ghost-cell-containing lesions (pilomatricoma, adamantinomatous craniopharyngioma, COC, ghost cell odontogenic carcinoma and, more recently, AA) (Figure 1). 7,19 Nuclear betacatenin accumulation is often evidenced by IHC, 26 being regarded as a surrogate marker for CTNNB1 mutations. However, such an assumption needs to be critically interpreted, as immunohistochemical positivity may occur in the absence of such mutations.…”

Section: Dentinogenic Ghost Cell Tumourmentioning

confidence: 99%

See 4 more Smart Citations

The molecular basis of odontogenic cysts and tumours

Gomes

Bastos

Guimarães

et al. 2023

J Oral Pathology Medicine

Self Cite

View full text Add to dashboard Cite

The advances in molecular technologies have allowed a better understanding of the molecular basis of odontogenic cysts and tumours. PTCH1 mutations have been reported in a high proportion of odontogenic keratocyst. BRAF p.V600E are recurrent in ameloblastoma and KRAS p.G12V/R in adenomatoid odontogenic tumour, dysregulating the MAPK/ERK pathway. Notably, BRAF p.V600E is also detected in ameloblastic carcinoma, but at a lower frequency than in its benign counterpart ameloblastoma. Recently, adenoid ameloblastoma has been shown to be BRAF wild-type and to harbour CTNNB1 (β-catenin gene) mutations, further suggesting that it is not an ameloblastoma subtype. CTNNB1 mutations also occur in other ghost-cellcontaining tumours, including calcifying odontogenic cysts, dentinogenic ghost cell tumours and odontogenic carcinoma with dentinoid, but the link between CTNNB1 mutations and ghost cell formation in these lesions remains unclear. Regarding mixed tumours, BRAF p.V600E has been reported in a subset of ameloblastic fibromas, ameloblastic-fibrodentinomas and fibro-odontomas, in addition to ameloblastic fibrosarcoma. Such mutation-positivity in a subset of samples can be helpful in differentiating some of these lesions from odontoma, which is BRAF-wild-type. Recently, FOS rearrangements have been reported in cementoblastoma, supporting its relationship with osteoblastoma. Collectively, the identification of recurrent mutations in these aforementioned lesions has helped to clarify their molecular basis and to better understand the interrelationships between some tumours, but none of these genetic abnormalities is diagnostic. Since the functional effect of pathogenic mutations is context and tissue-dependent, a clear role for the reported mutations in odontogenic cysts and tumours in their pathogenesis remains to be elucidated.

show abstract