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Ameloblastoma: A Review of Recent Molecular Pathogenetic Discoveries.

Brown NA, Betz BL - Biomark Cancer (2015)

Bottom Line: Ameloblastoma is an odontogenic neoplasm whose molecular pathogenesis has only recently been elucidated.The discovery of recurrent activating mutations in FGFR2, BRAF, and RAS in a large majority of ameloblastomas has implicated dysregulation of MAPK pathway signaling as a critical step in the pathogenesis of this tumor.Some degree of controversy exists regarding the role of mutations affecting the sonic hedgehog (SHH) pathway, specifically Smoothened (SMO), which have been postulated to serve as either an alternative pathogenetic mechanism or secondary mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.

ABSTRACT
Ameloblastoma is an odontogenic neoplasm whose molecular pathogenesis has only recently been elucidated. The discovery of recurrent activating mutations in FGFR2, BRAF, and RAS in a large majority of ameloblastomas has implicated dysregulation of MAPK pathway signaling as a critical step in the pathogenesis of this tumor. Some degree of controversy exists regarding the role of mutations affecting the sonic hedgehog (SHH) pathway, specifically Smoothened (SMO), which have been postulated to serve as either an alternative pathogenetic mechanism or secondary mutations. Here, we review recent advances in our understanding of the molecular pathogenesis of ameloblastoma as well as the diagnostic, prognostic, and therapeutic implications of these discoveries.

No MeSH data available.


Related in: MedlinePlus

Relationship between the anatomic location and mutation frequency in ameloblastoma based on all studies in which BRAF, RAS, FGFR2, and SMO were evaluated.10–13,40
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Related In: Results  -  Collection


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f4-bic-suppl.2-2015-019: Relationship between the anatomic location and mutation frequency in ameloblastoma based on all studies in which BRAF, RAS, FGFR2, and SMO were evaluated.10–13,40

Mentions: The mutation profile of ameloblastomas correlates with histopathology, location (Fig. 4), age at diagnosis, and prognosis (Fig. 5). As stated earlier, Sweeney et al11 postulated that BRAF-mutated and SMO-mutated tumors represent two distinct molecular subtypes with ameloblastoma with different clinicopathologic features including location, histologic pattern (follicular versus plexiform), and possibly prognosis. The former two showed statistically significant associations with genotype (BRAF-mutated vs SMO-mutated). However, in the larger series from Brown et al,12 these associations correlated better with the presence or absence of the BRAF mutation rather than the presence of SMO mutations, which were found in only a minority of BRAF wild-type tumors (37%). BRAF mutations were shown to occur much more frequently in the mandible and only rarely in the maxilla (5.6%), while 43% of BRAF wild-type tumors arose in the maxilla. This trend was not specific for SMO-mutated tumors; indeed, 64% of BRAF wild-type, SMO wild-type tumors also arose in the maxilla.


Ameloblastoma: A Review of Recent Molecular Pathogenetic Discoveries.

Brown NA, Betz BL - Biomark Cancer (2015)

Relationship between the anatomic location and mutation frequency in ameloblastoma based on all studies in which BRAF, RAS, FGFR2, and SMO were evaluated.10–13,40
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4597444&req=5

f4-bic-suppl.2-2015-019: Relationship between the anatomic location and mutation frequency in ameloblastoma based on all studies in which BRAF, RAS, FGFR2, and SMO were evaluated.10–13,40
Mentions: The mutation profile of ameloblastomas correlates with histopathology, location (Fig. 4), age at diagnosis, and prognosis (Fig. 5). As stated earlier, Sweeney et al11 postulated that BRAF-mutated and SMO-mutated tumors represent two distinct molecular subtypes with ameloblastoma with different clinicopathologic features including location, histologic pattern (follicular versus plexiform), and possibly prognosis. The former two showed statistically significant associations with genotype (BRAF-mutated vs SMO-mutated). However, in the larger series from Brown et al,12 these associations correlated better with the presence or absence of the BRAF mutation rather than the presence of SMO mutations, which were found in only a minority of BRAF wild-type tumors (37%). BRAF mutations were shown to occur much more frequently in the mandible and only rarely in the maxilla (5.6%), while 43% of BRAF wild-type tumors arose in the maxilla. This trend was not specific for SMO-mutated tumors; indeed, 64% of BRAF wild-type, SMO wild-type tumors also arose in the maxilla.

Bottom Line: Ameloblastoma is an odontogenic neoplasm whose molecular pathogenesis has only recently been elucidated.The discovery of recurrent activating mutations in FGFR2, BRAF, and RAS in a large majority of ameloblastomas has implicated dysregulation of MAPK pathway signaling as a critical step in the pathogenesis of this tumor.Some degree of controversy exists regarding the role of mutations affecting the sonic hedgehog (SHH) pathway, specifically Smoothened (SMO), which have been postulated to serve as either an alternative pathogenetic mechanism or secondary mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.

ABSTRACT
Ameloblastoma is an odontogenic neoplasm whose molecular pathogenesis has only recently been elucidated. The discovery of recurrent activating mutations in FGFR2, BRAF, and RAS in a large majority of ameloblastomas has implicated dysregulation of MAPK pathway signaling as a critical step in the pathogenesis of this tumor. Some degree of controversy exists regarding the role of mutations affecting the sonic hedgehog (SHH) pathway, specifically Smoothened (SMO), which have been postulated to serve as either an alternative pathogenetic mechanism or secondary mutations. Here, we review recent advances in our understanding of the molecular pathogenesis of ameloblastoma as well as the diagnostic, prognostic, and therapeutic implications of these discoveries.

No MeSH data available.


Related in: MedlinePlus