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Molecular alterations in basal cell carcinoma subtypes

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, STE...

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Autores principales: Di Nardo, Lucia, Pellegrini, Cristina, Di Stefani, Alessandro, Ricci, Francesco, Fossati, Barbara, Del Regno, Laura, Carbone, Carmine, Piro, Geny, Corbo, Vincenzo, Delfino, Pietro, De Summa, Simona, Maturo, Maria Giovanna, Rocco, Tea, Tortora, Giampaolo, Fargnoli, Maria Concetta, Peris, Ketty
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225846/
https://www.ncbi.nlm.nih.gov/pubmed/34168209
http://dx.doi.org/10.1038/s41598-021-92592-3
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author Di Nardo, Lucia
Pellegrini, Cristina
Di Stefani, Alessandro
Ricci, Francesco
Fossati, Barbara
Del Regno, Laura
Carbone, Carmine
Piro, Geny
Corbo, Vincenzo
Delfino, Pietro
De Summa, Simona
Maturo, Maria Giovanna
Rocco, Tea
Tortora, Giampaolo
Fargnoli, Maria Concetta
Peris, Ketty
author_facet Di Nardo, Lucia
Pellegrini, Cristina
Di Stefani, Alessandro
Ricci, Francesco
Fossati, Barbara
Del Regno, Laura
Carbone, Carmine
Piro, Geny
Corbo, Vincenzo
Delfino, Pietro
De Summa, Simona
Maturo, Maria Giovanna
Rocco, Tea
Tortora, Giampaolo
Fargnoli, Maria Concetta
Peris, Ketty
author_sort Di Nardo, Lucia
collection PubMed
description 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.
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spelling pubmed-82258462021-07-02 Molecular alterations in basal cell carcinoma subtypes Di Nardo, Lucia Pellegrini, Cristina Di Stefani, Alessandro Ricci, Francesco Fossati, Barbara Del Regno, Laura Carbone, Carmine Piro, Geny Corbo, Vincenzo Delfino, Pietro De Summa, Simona Maturo, Maria Giovanna Rocco, Tea Tortora, Giampaolo Fargnoli, Maria Concetta Peris, Ketty Sci Rep Article 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. Nature Publishing Group UK 2021-06-24 /pmc/articles/PMC8225846/ /pubmed/34168209 http://dx.doi.org/10.1038/s41598-021-92592-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Di Nardo, Lucia
Pellegrini, Cristina
Di Stefani, Alessandro
Ricci, Francesco
Fossati, Barbara
Del Regno, Laura
Carbone, Carmine
Piro, Geny
Corbo, Vincenzo
Delfino, Pietro
De Summa, Simona
Maturo, Maria Giovanna
Rocco, Tea
Tortora, Giampaolo
Fargnoli, Maria Concetta
Peris, Ketty
Molecular alterations in basal cell carcinoma subtypes
title Molecular alterations in basal cell carcinoma subtypes
title_full Molecular alterations in basal cell carcinoma subtypes
title_fullStr Molecular alterations in basal cell carcinoma subtypes
title_full_unstemmed Molecular alterations in basal cell carcinoma subtypes
title_short Molecular alterations in basal cell carcinoma subtypes
title_sort molecular alterations in basal cell carcinoma subtypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225846/
https://www.ncbi.nlm.nih.gov/pubmed/34168209
http://dx.doi.org/10.1038/s41598-021-92592-3
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