Paula Boaventura1, Dina Pereira2, Adélia Mendes3, Rui Batista4, André Ferreira da Silva5, Isabel Guimarães6, Mrinalini Honavar7, José Teixeira-Gomes8, José Manuel Lopes9, Valdemar Máximo10, Paula Soares11. 1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: mboaventura@ipatimup.pt. 2. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: dina_pereira86@hotmail.com. 3. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: mmendes@ipatimup.pt. 4. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: rbatista@ipatimup.pt. 5. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: asilva@ipatimup.pt. 6. Hospital Pedro Hispano, Rua Dr. Eduardo Torres, 4464-513 Senhora da Hora, Portugal. Electronic address: Isabel.Guimaraes@ulsm.min-saude.pt. 7. Hospital Pedro Hispano, Rua Dr. Eduardo Torres, 4464-513 Senhora da Hora, Portugal. Electronic address: Mrinalini.Honavar@ulsm.min-saude.pt. 8. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal. Electronic address: jose@teixeiragomes.pt. 9. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal; Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: jmlopes@ipatimup.pt. 10. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal; Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: vmaximo@ipatimup.pt. 11. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, R. Roberto Frias s/n, 4200-465 Porto, Portugal; Medical Faculty, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. Electronic address: psoares@ipatimup.pt.
Abstract
BACKGROUND: Basal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human tumors, but their occurrence in BCC is poorly documented. OBJECTIVE: The purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC. METHODS: 228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients. RESULTS: The infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation. CONCLUSIONS: Our results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients.
BACKGROUND:Basal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many humantumors, but their occurrence in BCC is poorly documented. OBJECTIVE: The purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC. METHODS: 228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients. RESULTS: The infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation. CONCLUSIONS: Our results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients.
Authors: Stefanie L Thorsness; Azael Freites-Martinez; Michael A Marchetti; Cristian Navarrete-Dechent; Mario E Lacouture; Emily S Tonorezos Journal: J Natl Compr Canc Netw Date: 2019-03-01 Impact factor: 11.908
Authors: António Castanheira; Maria João Vieira; Mafalda Pinto; Carolina Dias; Luísa Prada; Sofia Macedo; Margarida Sá Fernandes; Fortunato Vieira; Paula Soares; Alberto Mota; José Manuel Lopes; Paula Boaventura Journal: Sci Rep Date: 2021-05-17 Impact factor: 4.379