Genetic alterations in thyroid tumors from patients irradiated in childhood for tinea capitis treatment

Eur J Endocrinol. 2013 Oct 3;169(5):673-9. doi: 10.1530/EJE-13-0543. Print 2013 Nov.

Abstract

Objective: Exposure to ionizing radiation at young age is the strongest risk factor for the occurrence of papillary thyroid carcinoma (PTC). RET/PTC rearrangements are the most frequent genetic alterations associated with radiation-induced PTC, whereas BRAF and RAS mutations and PAX8-PPARG rearrangement have been associated with sporadic PTC. We decided to search for such genetic alterations in PTCs of patients subjected in childhood to scalp irradiation.

Design: We studied 67 thyroid tumors from 49 individuals irradiated in childhood for tinea capitis scalp epilation: 36 malignant (12 cases of conventional PTC (cPTC), two cPTC metastases, 20 cases of follicular variant PTC (FVPTC), one oncocytic variant of PTC and one follicular carcinoma) and 31 follicular thyroid adenomas.

Methods: The lesions were screened for the BRAF(V600E) and NRAS mutations and for RET/PTC and PAX8-PPARG rearrangements.

Results: BRAF(V600E) mutation was detected in seven of 14 (50%) cPTC and two of 20 FVPTC (10%) (P=0.019). NRAS mutation was present in one case of FVPTC (5%). RET/PTC1 rearrangement was found, by RT-PCR, in one of 17 cases (5.9%) and by fluorescence in situ hybridization in two of six cases (33%). PAX8-PPARG rearrangement was not detected in any carcinoma. None of the follicular adenomas presented any of the aforementioned genetic alterations.

Conclusions: The prevalence of BRAF(V600E) mutation in our series is the highest reported in series of PTCs arising in radiation-exposed individuals. The prevalence of RET/PTC1 rearrangement fits with the values recently described in a similar setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Carcinoma, Papillary / epidemiology
  • Carcinoma, Papillary / genetics*
  • Child
  • Cohort Studies
  • Female
  • GTP Phosphohydrolases / genetics
  • Gene Rearrangement
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Mutation / radiation effects
  • PAX8 Transcription Factor
  • PPAR gamma / genetics
  • Paired Box Transcription Factors / genetics
  • Prevalence
  • Proto-Oncogene Proteins B-raf / genetics
  • Radiotherapy / adverse effects*
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Thyroid Neoplasms / epidemiology
  • Thyroid Neoplasms / genetics*
  • Tinea Capitis / complications*
  • Tinea Capitis / radiotherapy*

Substances

  • Membrane Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • PPAR gamma
  • Paired Box Transcription Factors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human