A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour. We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.9% and 45.6% of BCCs, respectively. A high mutation rate was also detected in CSMD1 (63.2%), NOTCH1 (43.8%) and DPP10 (35.1%), and frequent non-coding mutations were identified in TERT (57.9%) and DPH3 promoter (49.1%). CSMD1 mutations significantly co-occurred with TP53 changes (p = 0.002). A significant association was observed between the superficial type of BCC and PTCH1 (p = 0.018) and NOTCH1 (p = 0.020) mutations. In addition, PTCH1 mutations were significantly associated with intermittent sun exposure (p = 0.046) and the occurrence of single lesions (p = 0.021), while NOTCH1 mutations were more frequent in BCCs located on the trunk compared to the head/neck and extremities (p = 0.001). In conclusion, we provide further insights into the molecular alterations underlying the tumorigenic mechanism of superficial and nodular BCCs with a view towards novel rationale-based therapeutic strategies.

除了 Hedgehog 通路外，许多基因也与 BCC 的发病机制有关，Hedgehog 通路已知会导致这种肿瘤的发生。我们进行了深入的13 BCC-相关基因（分析CSMD1，CSMD2，DPH3促进R，PTCH1，SMO，GLI1，NOTCH1，NOTCH2，TP53，ITIH2，DPP10，STEAP4，TERT在57个BCC病变启动子）（26浅表和31 个结节）来自 55 名患者及其相应的血液样本。PTCH1和TP53突变分别在 71.9% 和 45.6% 的 BCC 中发现。在CSMD1 (63.2%)、NOTCH1 (43.8%) 和DPP10 (35.1%)中也检测到高突变率，并且在TERT中发现了频繁的非编码突变(57.9%) 和DPH3启动子 (49.1%)。CSMD1突变与TP53变化显着共同发生（p  = 0.002）。在 BCC 的浅表类型与PTCH1 ( p  = 0.018) 和NOTCH1 ( p  = 0.020) 突变之间观察到显着关联。此外，PTCH1突变与间歇性阳光照射（p  = 0.046）和单一病变的发生（p  = 0.021）显着相关，而与头颈部和四肢相比，位于躯干的 BCC 中NOTCH1突变更频繁（磷 = 0.001）。总之，我们提供了对浅表和结节性 BCC 致瘤机制的分子改变的进一步见解，以期制定新的基于理论的治疗策略。