RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics.
RET/PTC and PAX8/PPARγ chromosomal rearrangements in post-Chernobyl thyroid cancer and their association with iodine-131 radiation dose and other characteristics.
复制标题
DOI：
10.1002/cncr.27893
复制
发表时间：
2013-05-15
期刊：
影响因子：
6.2
通讯作者：
Nikiforov, Yuri E.
中科院分区：
文献类型：
--
作者：
Leeman-Neill, Rebecca J.;Brenner, Alina V.;Little, Mark P.;Bogdanova, Tetiana I.;Hatch, Maureen;Zurnadzy, Liudmyla Y.;Mabuchi, Kiyohiko;Tronko, Mykola D.;Nikiforov, Yuri E.
1986年切尔诺贝利核电站事故导致儿童接触I-131，导致反应堆周围地区乳头状甲状腺癌（PTC）发病率急剧上升。关于PTC基因突变与个体辐射剂量之间的关联的数据有限。我们对乌克兰一组<18岁的患者中诊断的62例PTC进行了突变分析。在1986年，接受了0.008-8.6戈伊的I-131甲状腺，并探讨了突变类型和I-131剂量和其他特征之间的关联。RET/PTC重排最常见（35%），其次是BRAF（15%）和RAS（8%）点突变。发现2例携带PAX 8/PPARγ重排的肿瘤。基于RET/PTC和PAX 8/PPARγ重排的线性二次模型，我们发现BRAF和RAS点突变与I-131剂量呈显著负相关，与I-131剂量呈显著凹相关，拐点为1.6戈伊，比值比为2.1。随着剂量的变化趋势在具有点突变和重排的肿瘤之间显著不同。与点突变相比，重排与居住在相对缺碘的日托米尔地区、暴露或手术时年龄较小以及男性相关。我们的研究结果首次证明了切尔诺贝利后肿瘤中PAX 8/PPARγ重排，并显示了点突变和染色体重排与I-131剂量和其他因素的不同关联。这些数据支持染色体重排（而非点突变）与I-131暴露之间的关系，并指出碘缺乏可能在这些患者中产生RET/PTC重排中发挥作用。
Childhood exposure to I-131 from the 1986 Chernobyl accident led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited. We performed mutational analysis of 62 PTCs diagnosed in a Ukrainian cohort of patients who were <18 y.o. in 1986 and received 0.008-8.6 Gy of I-131 to the thyroid and explored associations between mutation types and I-131 dose and other characteristics. RET/PTC rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ rearrangement were identified. We found a significant negative association with I-131 dose for BRAF and RAS point mutations and a significant concave association with I-131 dose, with an inflection point at 1.6 Gy and odds ratio 2.1, based on a linear-quadratic model for RET/PTC and PAX8/PPARγ rearrangements. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared to point mutations, rearrangements were associated with residence in the relatively iodine deficient Zhytomyr region, younger age at exposure or surgery, and male gender. Our results provide the first demonstration of PAX8/PPARγ rearrangements in post-Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with I-131 dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and I-131 exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients.
登录
查看更多内容
影响因子：
10.3
作者：
Cardis, E;Kesminiene, A;Williams, D
通讯作者：
Williams, D
影响因子：
5.8
作者：
Nikiforov, Yuri E.;Steward, David L.;Nikiforova, Marina N.
通讯作者：
Nikiforova, Marina N.
影响因子：
8
作者：
Mizuno, T;Iwamoto, KS;Hamatani, K
通讯作者：
Hamatani, K
影响因子：
5.6
作者：
Nikiforova, MN;Biddinger, PW;Nikiforov, YE
通讯作者：
Nikiforov, YE
影响因子：
5.8
作者：
Hayat, Matthew J.;Howlader, Nadia;Edwards, Brenda K.
通讯作者：
Edwards, Brenda K.