儿童期头癣治疗接受放射治疗的甲状腺肿瘤中的遗传改变。

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

机构信息

IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Dr Roberto Frias s/n, 4200-465 Porto, Portugal.

出版信息

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

DOI:10.1530/EJE-13-0543

PMID:23966419

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.

摘要

目的

年轻时接触电离辐射是甲状腺乳头癌（PTC）发生的最强危险因素。RET/PTC 重排是与辐射诱导的 PTC 最相关的最常见遗传改变，而 BRAF 和 RAS 突变以及 PAX8-PPARG 重排与散发性 PTC 相关。我们决定在儿童期接受头皮照射的 PTC 患者中寻找此类遗传改变。

设计

我们研究了 49 名因头癣头皮脱毛而在儿童期接受照射的个体的 67 个甲状腺肿瘤：36 个恶性肿瘤（12 例经典 PTC（cPTC）、2 例 cPTC 转移、20 例滤泡变体 PTC（FVPTC）、1 例 PTC 嗜酸细胞变体和 1 例滤泡癌）和 31 个滤泡状甲状腺腺瘤。

方法

对病变进行 BRAF(V600E)和 NRAS 突变以及 RET/PTC 和 PAX8-PPARG 重排的筛查。

结果

14 例 cPTC 中有 7 例（50%）和 20 例 FVPTC 中有 2 例（10%）（P=0.019）检测到 BRAF(V600E)突变。1 例 FVPTC 中有 NRAS 突变（5%）。通过 RT-PCR 在 17 例中的 1 例（5.9%）和通过荧光原位杂交在 6 例中的 2 例（33%）中发现 RET/PTC1 重排。在任何癌中均未检测到 PAX8-PPARG 重排。没有一个滤泡状腺瘤出现上述任何遗传改变。