Patient‐derived xenografts of a case of ameloblastic fibrodentinoma

Abstract

Objectives The establishment of animal models of xenotransplantation can contribute to the elucidation of the molecular pathogenesis of ameloblastic fibrodentinomas (AFD) and it also provides an opportunity for drug tests. We aimed to evaluate the possibility of AFD tumour growth in a patient‐derived xenograft (PDX) model. In addition, we characterized the human tumour and the PDXs. Materials and Methods A sample of a recurrent AFD was obtained and two fragments were contralaterally implanted subcutaneously in an 8‐week old female NUDE mouse. After 250 days, the PDXs were removed and submitted to histopathological and molecular analysis. Immunohistochemical reactions for Ki67 and the phosphorylated form of ERK1/2 were carried out in both, PDXs and human tumour, and the presence of BRAFV600E was assessed. Results From day 135 onwards, the PDXs presented a growth peak and remained stable until day 250. Histopathologically, the PDXs presented the same features of the patient’s tumour. Tumour cells exhibited Ki67 and pERK1/2 immunoexpression in the patient’s tumour and PDX. The AFD was wild‐type for BRAFV600E. Conclusion The PDX model recapitulated well the human tumour after a long implantation time, representing a possible model to study the AFD and other odontogenic tumours pathobiology.

Targeted Next-Generation Sequencing and Allele-Specific Quantitative PCR of Laser Capture Microdissected Samples Uncover Molecular Differences in Mixed Odontogenic Tumors

“…The patient-derived xenograft model was followed for 250 days, and it was observed to be tumorigenic and maintain morphologic characteristics of the primary tumor and MAPK jmdjournal.org -The Journal of Molecular Diagnostics pathway activation, together with cell proliferation activity similar to the human tumor. 21 Taking together the molecular data and the above described results, the authors conclude that at least a subset of those lesions diagnosed as AF, AFD, and AFO are molecularly distinct from OD, which does not support the assumption that these subsets represent progressive stages of odontoma development and suggests they should not be grouped together.…”

“…The BRAF mutation was detected in these mixed odontogenic tumors but was absent in all the OD cases studied. In a previous study by the authors' group, 21 the development of a recurrent AFD case (that did not previously show maturation after 6 years) was evaluated using a patient-derived xenograft model. The patient-derived xenograft model was followed for 250 days, and it was observed to be tumorigenic and maintain morphologic characteristics of the primary tumor and MAPK jmdjournal.org -The Journal of Molecular Diagnostics pathway activation, together with cell proliferation activity similar to the human tumor.…”