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.
Wei-Peng JiangZi-Han SimaHai-Cheng WangJian-Yun ZhangLi-Sha SunFeng ChenTie-Jun Li
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.
