TY - JOUR
T1 - Molecular alterations in basal cell carcinoma subtypes
AU - Di Nardo, Lucia
AU - Pellegrini, Cristina
AU - Di Stefani, Alessandro
AU - Ricci, Francesco
AU - Fossati, Barbara
AU - Del Regno, Laura
AU - Carbone, Carmine
AU - Piro, Geny
AU - Corbo, Vincenzo
AU - Delfino, Pietro
AU - De Summa, Simona
AU - Maturo, Maria Giovanna
AU - Rocco, Tea
AU - Tortora, Giampaolo
AU - Fargnoli, Maria Concetta
AU - Peris, Ketty
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Aged
KW - Carcinoma, Basal Cell
KW - Female
KW - Humans
KW - Male
KW - Mutation
KW - Neoplasms, Basal Cell
KW - Promoter Regions, Genetic
KW - Signal Transduction
KW - Skin Neoplasms
KW - Aged
KW - Carcinoma, Basal Cell
KW - Female
KW - Humans
KW - Male
KW - Mutation
KW - Neoplasms, Basal Cell
KW - Promoter Regions, Genetic
KW - Signal Transduction
KW - Skin Neoplasms
UR - http://hdl.handle.net/10807/197831
U2 - 10.1038/s41598-021-92592-3
DO - 10.1038/s41598-021-92592-3
M3 - Article
SN - 2045-2322
VL - 11
SP - 13206-N/A
JO - Scientific Reports
JF - Scientific Reports
ER -