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Sonic hedgehog signaling pathway. The upregulated and downregulated molecules of the pathway is shown according to the legend.
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Keratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity an...
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Context 1
... and 1 gene set was inhibited (nominal p-value < 0.05) (Table 2). Specifically, the Sonic hedgehog signaling (SHH/PTCH1) pathway was not found to be significantly differentially expressed between normal and tumor tissue. Closer examination of the SHH/PTCH1 pathway showed downregulation of PTCH1 and its downstream target GLI without changes to SHH (Fig. ...
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... Thus, all six sporadic OKCs were processed as one group in downstream bioinformatics analysis, in alignment with previous microarray-based studies. 3,4 Next, 2427 DEGs (1442 upregulated, 985 downregulated) between BCNS-associated OKCs and DFs were obtained and two discrete clusters of BCNSassociated OKCs or DFs were identified ( Figure 1B,C, Table S8). ...
... ,28 Finally, we observed a highly (80.5%) shared gene expression profile among primary and recurrent sporadic OKCs, and, thus, processed them as one group, in line with previous studies.3,4 The sample size of primary and recurrent subgroups, although sufficient for DEGs identification,8 might be considered as a study limitation. ...
Background:
Odontogenic keratocyst (OKC) is characterized by local aggressive behavior and a high recurrence rate, as well as the potential to develop in association with the Basal Cell Nevus Syndrome (BCNS). The aim of this study was to decode the gene expression program accompanying OKC phenotype.
Methods:
150-bp paired-end RNA-sequencing was applied on 6 sporadic and 6 BSCN-associated whole-tissue OKC samples in comparison to 6 dental follicles, coupled to bioinformatics and complemented by immunohistochemistry.
Results:
2,654 and 2,427 differentially expressed genes were captured to characterize the transcriptome of sporadic and BCNS-associated OKCs, respectively. Gene ontologies (GOs) related to "epidermis/skin development" and "keratinocyte/epidermal cell differentiation" were enriched among the upregulated genes (KRT10, NCCRP1, TP63, GRHL3, SOX21), while "extracellular matrix (ECM) organization" (ITGA5, LOXL2) and "odontogenesis" (MSX1, LHX8) GOs were overrepresented among the downregulated genes in OKC. Interestingly, upregulation of various embryonic stem cells (ESCs) markers (EPHA1, SCNN1A) and genes committed in cellular reprogramming (SOX2, KLF4, OVOL1, IRF6, TACSTD2, CDH1) was found in OKC. These findings were highly shared between sporadic and BCNS-associated OKCs. Immunohistochemistry verified SOX2, KLF4, OVOL1, IRF6, TACSTD2/TROP2, CDH1/E-cadherin, and p63 expression predominantly in the OKC suprabasal epithelial layers.
Conclusion:
The OKC transcriptomic profile is characterized by a prominent epidermal and dental epithelial fate, a repressed dental mesenchyme fate combined with deregulated ECM organization, and enhanced stemness gene signatures. Thus, we propose a developed epidermis-like phenotype in the OKC suprabasal epithelial cells, established in parallel to a significant upregulation of marker genes related to ESCs and cellular reprogramming. This article is protected by copyright. All rights reserved.
... Thus, further research is warranted, including additional markers. Next-generation sequencing (NGS)-based studies that have the advantage of massive-inparallel delineation of the expression of thousands of genes may reveal new OKC-associated markers but up to date have been focused on sporadic OKC samples, while the BCNSassociated OKC gene expression program remains elusive [117][118][119]. A recent study on the proteomic profile of 5 OKCs that included one case diagnosed with BCNS, which is not followed by comments related to the differentially expressed proteins between sporadic and BCNS-associated OKCs, was provided [120]. ...
Objectives
To provide a systematic review of the literature on studies comparing the immunoprofile of nevoid basal cell carcinoma syndrome (BCNS)–associated and sporadic odontogenic keratocysts (OKCs), in order to identify markers that could accurately distinguish the two OKC subtypes.Materials and methodsWe searched MEDLINE/Pubmed, Web of Science, EMBASE via OVID, and grey literature for publications until December 28th, 2019, that compared the immunohistochemical expression of the two OKC subtypes. The studies were qualitatively assessed using the Critical Appraisal Tool for Case Series (Joana Briggs Institute). Sensitivity and specificity, positive and negative likelihood ratio, diagnostic odds ratio and area under the curve, and pooled estimates were calculated, using a random-effects model.ResultsSeventy-one studies were qualitatively analyzed; 61 markers were evaluated in one study and 32 in ≥ 2 studies. Twenty-five studies reported differential expression of 29 markers in the form of higher number of positive cells or greater staining intensity usually in BCNS-associated OKCs. Meta-analysis for bcl-2, Cyclin D1, CD56, CK18, p53, and PCNA showed that none of those markers is distinguishable between BCNS-associated and sporadic OKCs, in a 95% confidence interval. The risk of bias was high in 34 studies, moderate in 22, and low in 15.Conclusions
The present systematic review and meta-analysis uncovered that, although several immunohistochemical markers might characterize the OKC phenotype, they cannot discriminate between the BCNS-associated and sporadic OKCs.Clinical relevanceThis study highlighted the requirement for additional screening for markers by immunohistochemistry, preferentially coupled to alternative diagnostic applications such as genomics technologies.
... 26 In contrast, a comparative genome-wide expression analysis between sporadic OKCs and distinct odontogenic tissues ("dentome") reported the existence of different molecular subtypes of this lesion, according to the expression of 60 genes involved in odontogenesis. 66 Most of the samples were found to be more closely related to secretory ameloblasts. Although OKC subtypes had differences in several biological processes, including activation of AKT and MAPK pathways, common alterations compared with the reference were also found in the 2 subtypes. ...
... Notably, PTCH1 and GLI1 had diminished levels in both clusters, even though the SHH pathway was not differentially regulated between the odontogenic cyst and "dentome." 66 The conflicting results of these reports might be associated with the use of different types of samples as control, besides sample processing and data analysis. ...
Odontogenic cysts and tumors are heterogeneous lesions, originating from elements or remnants of the odontogenic apparatus. Although the majority of these lesions are benign and never undergo malignant transformation, rare malignant tumors may arise de novo or from benign precursors. The molecular basis of these lesions is still poorly understood. This article summarizes and discusses studies using small, medium, and large-scale and/or "-omic" techniques to describe the molecular characteristics of benign and malignant odontogenic lesions and briefly debates strategies to increase the use of "-omic" and multi-omic approaches or integrative analyses in the research of these lesions. A comprehensive understanding of the molecular aspects of odontogenic lesions by using large-scale approaches will enable us to refine the classification of this heterogeneous group of disorders and provide more accurate biomarkers for precise diagnosis, prognosis, and development of molecular tools in the management of patients with these conditions.
... No presente estudo, o perfil epidemiológico do grupo de OKC encontrado demonstrou diferença entre os sexos acometidos por esta lesão, sendo o sexo feminino o mais acometido (70%), em conformidade com o estudo de Hormozi et al (2016) No entanto, outros autores relataram predileção pelo sexo masculino (ANTUNES et al., 2007;HORMOZI et al., 2016). Em relação à faixa etária, indivíduos com idade entre a 1ª e a 2ª década de vida foram os mais acometidos nesta pesquisa (80%). ...
... Nesta pesquisa fica evidente, também, que somente cerca de 30% dos estudantes brancos e aproximadamente 50% dos não brancos vieram de escola pública, demonstrando que quanto maior a renda, maior a probabilidade de o indivíduo estudar em escola privada. Estes autores afirmam que a política de bônus adicional, adotada pela UFMG no período estudado, fez com que alunos que não entrariam nesta universidade passaram a ingressar nela.Os dados do terceiro ciclo do ENADE(2016) mostram que há uma forte correlação entre renda familiar, origem escolar, cor, trabalho e escolaridade dos pais. Cursos identificados como os mais brancos, com estudantes mais ricos, que não trabalham e que vêm de escola de ensino médio privado são também os cursos que têm a maioria de estudantes que vêm de famílias cujo pai tem escolaridade superior. ...
ABSTRACT: Introduction: Few studies have presented the impact on the quality of
life of patients undergoing rapid maxillary expansion. Considering the relevance of this
factor, the present study aimed to evaluate, during the expansion, the impact caused
by 2 types of appliances on the quality of life of patients. Material and methods:
Thirty-four patients with posterior crossbite and maxillary deficiency were selected and
randomly divided into two groups: G1: treatment with hybrid expander (tooth-boneborne)
and G2: treatment with conventional expanders (tooth-borne). ). The OHIP-
14 instrument was applied to patients aged 11 to 14 years, female and male, in two
moments: before the beginning of treatment (T0) and in the first week of activation of
the expanders (T1). Descriptive statistics were performed, and the t-test for paired
measurements was chosen to compare the quality of life at 2 moments (T0 and T1).
The significance level of 5% was adopted. Results: Significant differences were found
between T0 and T1 in both groups in the domains of functional limitation and physical
pain. In addition, group 2 (hyrax) showed a statistically significant difference in questions
of the physical disability domain. Conclusion: both Hyrax Hybrid and Hyrax can cause
pain and discomfort, causing a negative impact on the patient’s quality of life during
treatment. These devices can disrupt speech, change the taste of food and prejudice
feed. In group 2 (Hyrax) the impact was superior, higher scores were found regarding
discomfort during feeding, and meal interruption. When it comes to quality of life during
maxillary expansion, the Hyrax hybrid appliance is the most suitable.
... As LINE-1 hypomethylation is considered a progressive process during tumor development, it might be an important epigenetic event leading to the aggressiveness of ameloblastomas (Kitkumthorn and Mutirangura, 2010). Hu et al (2016) compared the transcriptome of KCOT utilizing whole-genome microarray with the 'dentome' and identified two different molecular subtypes operative in non-syndromic KCOTs. In one molecular subtype, the phosphoinositide 3-kinase/AK strain transforming (PI3K/ AKT) pathway was functional, and in the other, mitogenactivated protein kinase (MAPK) pathway was active. ...
... The former has a gene expression profile similar to secretory ameloblast (s-KCOT), while the latter had a gene expression profile resembling odontoblast (o-KCOT). The common downregulated genes in these distinct molecular subtypes were PCTH-1 and GLI-1 (Hu et al, 2016). The authors concluded that even though the phenotype was same (both were KCOT), yet their response to therapy may be different (based on molecular pathway operative, i.e., their genotypes were different). ...
Laser capture microdissection (LCM) is a high end research and diagnostic technology that helps in obtaining pure cell populations for the purpose of cell or lesion specific genomic and proteomic analysis. Literature search on the application of LCM in oral tissues was made through PUBMED. There is ample evidence to substantiate the utility of LCM in understanding the underlying molecular mechanism involving an array of oral physiological and pathological processes, including odontogenesis, taste perception, eruptive tooth movement, oral microbes, and cancers of the mouth and jaw tumors. This review is aimed at exploring the potential application of LCM in oral tissues as a high-throughput tool for integrated oral sciences. The indispensable application of LCM in the construction of lesion specific genomic libraries with emphasis on some of the novel molecular markers thus discovered is also highlighted. This article is protected by copyright. All rights reserved.
... 30 Recently, microdissected OKC epithelial tissue from 20 sporadic cases was included in transcriptome analysis via whole-genome microarray. 31 The authors reported that PTCH1 and GLI were downregulated. This last finding is in contrast with previous studies that used OKCs, medulloblastomas and skin tumors, which showed PTCH1 loss and GLI1 overexpression instead of downregulation. ...
The odontogenic keratocyst (OKC) is a cystic lesion, lined by uniformly-thickened parakeratinized epithelium. Some lesions are large and tend to recur after surgical treatment. The neoplastic nature of OKCs remains a matter of dispute. It is known that some sporadic OKCs harbor PTCH1 mutations, and via the dissection of cyst epithelium, these mutations were demonstrated to occur much more frequently than previously thought. In addition to the classical PTCH1 mutations, Hedgehog pathway disturbance and Bcl-2 protein overexpression, as detected via genome-wide expression analysis of OKCs, have been published. Changes in DNA methylation patterns and alterations in microRNA expression levels have recently been reported in these lesions. We reviewed the molecular mechanisms that underlie the pathogenesis of OKCs as described over the past few years and explored the molecular alterations that can be therapeutically targeted. This article is protected by copyright. All rights reserved.
This chapter provides a brief review of some of the more common of pathological entities: tooth demineralization, dental caries, root resorption, odontogenic cysts, odontogenic neoplasms, and nonodontogenic tumors of the jaw. A substantial number of additional nonodontogenic cysts, pseudocysts, and tumors can also occur in the jaws. Among these is a process unique to the jaws: the central giant cell lesion (CGCL). Odontogenic cysts and neoplasms originate in the tooth‐bearing areas of the jaws, and are characterized by replacement of bone by soft tissue or, less commonly, a mixture of soft and hard tissue. In the absence of secondary infection or significant expansion, odontogenic cysts and tumors typically cause few symptoms and are usually identified during routine dental radiographic examination. Regardless of the treatment approach selected, patients with a history of odontogenic keratocyst (OKC) should be followed radiographically for an indefinite period, as recurrences have been documented even decades after treatment.
Amelogenin (AMEL), the major structural protein of the enamel organic matrix, constitutes more than 90% of the
enamel’s protein content, Aberrations of amelogenin are thought to be involved in the oncogenesis of odontogenic
epithelium. The expression of amelogenin is possibly an indicator of differentiation of epithelial cells in the odontogenic
tumors. Aim of the study: Investigating the expression of amelogenin in some odontogenic tumors, using an
anti-amelogenin polyclonal antibody, and then compare it with AMEL expression in tooth buds as control. Materials
and Methods: study sample consisted of 10 formalin-fixed, paraffin- embedded specimens of ameloblastoma,
10 Keratocystic odontogenic tumors, and 10 tooth buds were conventionally stained with hematoxylin-eosin and
immunohistochemically with AMEL polyclonal antibody. Results: All of the odontogenic tumors expressed AMEL
in the epithelial component, Intensity of expression in ameloblastoma and Keratocystic odontogenic tumor was lower,
compared with tooth buds, Statistical analysis indicated a significant differences between the tumors and tooth buds.
Conclusion: Amelogenin can be used as a marker for odontogenic epithelium, and the expression of amelogenin is
possibly an indicator of epithelial cells differentiation in the odontogenic tumors, and therefore in prediction of the
histological behavior of odontogenic tumors.
Most of the odontogenic keratocysts show an indolent behaviour like non-neoplastic lesions. For this reason, the odontogenic keratocyst was reclassified within the odontogenic cysts category in the WHO 2017 classification. Some odontogenic keratocysts may contain satellite cysts or solid squamoid islands within their wall. Recently, a solid form of odontogenic keratocyst has also been described which is composed entirely of multiple epithelial islands and small cysts in a collagenous stroma. The true nature of this variant is unclear yet.
In this article, we present a series of 204 odontogenic keratocyst cases. Clinical and histologic findings of the cases in this series were described. These were also categorised according to the presence of satellite lesions. Additionally, the features of two cases of the solid form of odontogenic keratocysts were compared with those of the previous reports and other histologically similar odontogenic lesions. Current evidence suggests that this variant may be neoplastic and it differs from other odontogenic keratocysts, at least histologically. We believe diagnosing a solid lesion as a cyst is counterintuitive and the term “keratocystic odontogenic tumour” better describes this particular variant.
