Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas

J Dermatol Sci. 2014 Jan;73(1):31-9. doi: 10.1016/j.jdermsci.2013.09.002. Epub 2013 Sep 10.

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.

Keywords: BCC; Basal cell carcinoma; D-Loop; Histological subtype; Radiation; Tinea capitis; basal cell carcinoma; mitochondrial; mt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / pathology
  • Case-Control Studies
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / radiation effects*
  • Dose-Response Relationship, Radiation
  • Female
  • Hair Removal / adverse effects*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness
  • Neoplasms, Radiation-Induced / genetics*
  • Neoplasms, Radiation-Induced / pathology
  • Nucleic Acid Conformation
  • Phenotype
  • Registries
  • Risk Factors
  • Scalp / pathology
  • Scalp / radiation effects*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Tinea Capitis / microbiology
  • Tinea Capitis / radiotherapy*

Substances

  • DNA, Mitochondrial