Characteristics of molecular abnormalities in thyroid cancers from atomic bomb survivors

原子弹幸存者甲状腺乳头状癌（PTC）中的RET/PTC重排：尽管通过RT-PCR在89.5%的PTC中微管蛋白mRNA的表达是明显的，但在任何病例中均未检测到RET/PTC 1或PTC 3。我们首次证实了RET癌基因扩增的情况下，未分化甲状腺癌从A-曾因甲状腺癌接受过131 I内照射治疗的原子弹幸存者。RET扩增也被观察到在辐射诱导的乳头状甲状腺癌和分化不良的甲状腺癌，这表明参与基因组的不稳定性在甲状腺carcinogenesic. The基因组不稳定性在甲状腺滤泡上皮从原子弹幸存者：53 BP 1焦点形成的水平显着高于正常滤泡细胞的癌症。这些53 BP 1病灶与癌细胞中的上游pATM和下游p53分子共定位。原子弹爆炸幸存者PTC中BRAF突变：14.9%的PTC中检测到热点突变BRAF T1799 A，其余为野生型。原子弹辐射与BRAF突变无明显相关性。PTC中RET扩增与基因组不稳定性：PTC中RET扩增仅见于辐射诱导和高级别病例。在甲状腺癌发生过程中，53 BP 1在滤泡性腺瘤中形成灶状，其表达呈异常型，并伴有间变性转化。因此，基因组不稳定性可能在早期阶段被诱导，并随着肿瘤发生的进展而加速。53 BP 1在辐射诱导的PTC中的表达类型为异常型，表明RET扩增中基因组不稳定性增加。

RET/PTC rearrangement in papillary thyroid cancers (PTC) from A-bomb survivors : Although the expression of tubulin mRNA was evident in 89.5% of PTC by RT-PCR, neither RET/PTC1 nor PTC3 was detected in any cases.FISH analysis for RET in PTC : We firstly demonstrated amplification of RET oncogene in a case of anaplastic thyroid cancer from A-bomb survivors who received internal irradiation therapy with 131I for previous thyroid cancer. RET amplification was also observed in radiation-induced papillary thyroid cancers and poorly differentiated thyroid cancers, suggesting the involvement of genomic instability during thyroid carcinogenesis.Genomic instability in thyroid follicular epithelium from A-bomb survivors: The level of 53BP1 focus formation was significantly higher in cancers than normal follicular cells. These 53BP1 foci co-localized with upper stream pATM and downstream p53 molecules in cancer cells. A low level of 53BP1 foci formation could be detected also in follicular epithelium surrounding tumor, suggesting an initial stage during thyroid carcinogenesis.BRAF mutation in PTC from A-bomb survivors : A hot spot point mutation BRAF T1799A was detected in 14.9% of PTC, while others were wild type. No significant association was revealed between A-bomb radiation and BRAF mutation.RET amplification in PTC and genomic instability : RET amplification in PTC was only found in radiation-induced and high grade cases. During thyroid carcinogenesis, 53BP1 foci formation could be observed in follicular adenoma, and its expression altered into abnormal type with anaplastic transformation. Thus, genomic instability might be induced at the early stage and accelerated with progression of tumorigenesis. The type of 53BP1 expression in radiation-induced PTC was abnormal type, suggesting involvement of increased genomic instability in RET amplification.