Keratocystic odontogenic tumors (KCOT) are benign, locally aggressive intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel density (MVD) than dentigerous cysts (DC) and normal oral m...Keratocystic odontogenic tumors (KCOT) are benign, locally aggressive intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel density (MVD) than dentigerous cysts (DC) and normal oral mucosa. To identify genes in the stroma of KCOT involved in tumor development and progression, RNA sequencing (RNA-Seq) was performed using samples from KCOT and primary stromal fibroblasts isolated from gingival tissues. Seven candidate genes that possess a function potentially related to KCOT progression were selected and their expression levels were confirmed by quantitative PCR, immunohistochemistry and enzyme-linked immunosorbent assay. Expression of lysyl oxidase-like 4 (LOXL4), the only candidate gene that encodes a secreted protein, was enhanced at both the mRNA and protein levels in KCOT stromal tissues and primary KCOT stromal fibroblasts compared to control tissues and primary fibroblasts (P〈0.05). In vitro, high expression of LOXL4 could enhance proliferation and migration of the human umbilical vein endothelial cells (HUVECs). There was a significant, positive correlation between LOXL4 protein expression and MVD in stroma of KCOT and control tissues (r=0.882). These data suggest that abnormal expression of LOXL4 of KCOT may enhance angiogenesis in KCOT, which may help to promote the locally aggressive biological behavior of KCOT.展开更多
Aim To clarify the role of PTCH in patients with NBCCS- related and non-sydromic keratocystic odontogenic tumors. Methodology Mutation analysis was undertaken in 8 sporadic and 4 NBCCS-associated KCOTs. Results Four n...Aim To clarify the role of PTCH in patients with NBCCS- related and non-sydromic keratocystic odontogenic tumors. Methodology Mutation analysis was undertaken in 8 sporadic and 4 NBCCS-associated KCOTs. Results Four novel and two known mutations were identifled in 2 sporadic and 3 syndromic cases, two of which being germline mutations (c.2179delT, c.2824delC) and 4 somatic mutations (c.3162dupG, c.1362-1374dup, c.1012 C〉T, c.403C〉T). Conclusion Our findings suggest that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic KCOTs.展开更多
First described by Philipsen in 1956, the odontogenic keratocyst is characterized by a large squamous keratinization of its border, an aggressive growth and a high recurrent rate. It is now designated by the World Hea...First described by Philipsen in 1956, the odontogenic keratocyst is characterized by a large squamous keratinization of its border, an aggressive growth and a high recurrent rate. It is now designated by the World Health Organization as a keratocystic odontogenic tumour (KOT). Clinically, the KOT is manifested by an asymptomatic growth. Radiographically, it appears as a well-defined uni-locular or multilocular osteolytic lesion. The diagnostic approach is based on a combined analysis of the medical history, the clinical appearance and the radiographic appearance. The diagnosis may be confirmed by the anatomical pathology report. Finally, treatment consists of surgical excision and follow up is characterized by a high rate of recurrence. The authors report a case of keratocystic odontogenic tumor of the upper jaw and review the various diagnoses, therapeutics and follow up aspects of this type of tumors.展开更多
基金supported by the National Natural Science Foundation of China (grant nos. 81030018, 30872900 and 30901680)the Doctoral Fund of Ministry of Education of China (grant no. 20120001110043)
文摘Keratocystic odontogenic tumors (KCOT) are benign, locally aggressive intraosseous tumors of odontogenic origin. KCOT have a higher stromal microvessel density (MVD) than dentigerous cysts (DC) and normal oral mucosa. To identify genes in the stroma of KCOT involved in tumor development and progression, RNA sequencing (RNA-Seq) was performed using samples from KCOT and primary stromal fibroblasts isolated from gingival tissues. Seven candidate genes that possess a function potentially related to KCOT progression were selected and their expression levels were confirmed by quantitative PCR, immunohistochemistry and enzyme-linked immunosorbent assay. Expression of lysyl oxidase-like 4 (LOXL4), the only candidate gene that encodes a secreted protein, was enhanced at both the mRNA and protein levels in KCOT stromal tissues and primary KCOT stromal fibroblasts compared to control tissues and primary fibroblasts (P〈0.05). In vitro, high expression of LOXL4 could enhance proliferation and migration of the human umbilical vein endothelial cells (HUVECs). There was a significant, positive correlation between LOXL4 protein expression and MVD in stroma of KCOT and control tissues (r=0.882). These data suggest that abnormal expression of LOXL4 of KCOT may enhance angiogenesis in KCOT, which may help to promote the locally aggressive biological behavior of KCOT.
基金supported by Research Grants from the National Nature Science Foundation of China(30625044,30572048 and 30872900)Specialized Research Fund for the Doctoral Program of Higher Education(20050001110)
文摘Aim To clarify the role of PTCH in patients with NBCCS- related and non-sydromic keratocystic odontogenic tumors. Methodology Mutation analysis was undertaken in 8 sporadic and 4 NBCCS-associated KCOTs. Results Four novel and two known mutations were identifled in 2 sporadic and 3 syndromic cases, two of which being germline mutations (c.2179delT, c.2824delC) and 4 somatic mutations (c.3162dupG, c.1362-1374dup, c.1012 C〉T, c.403C〉T). Conclusion Our findings suggest that defects of PTCH are associated with the pathogenesis of syndromic as well as a subset of non-syndromic KCOTs.
文摘First described by Philipsen in 1956, the odontogenic keratocyst is characterized by a large squamous keratinization of its border, an aggressive growth and a high recurrent rate. It is now designated by the World Health Organization as a keratocystic odontogenic tumour (KOT). Clinically, the KOT is manifested by an asymptomatic growth. Radiographically, it appears as a well-defined uni-locular or multilocular osteolytic lesion. The diagnostic approach is based on a combined analysis of the medical history, the clinical appearance and the radiographic appearance. The diagnosis may be confirmed by the anatomical pathology report. Finally, treatment consists of surgical excision and follow up is characterized by a high rate of recurrence. The authors report a case of keratocystic odontogenic tumor of the upper jaw and review the various diagnoses, therapeutics and follow up aspects of this type of tumors.