Goldenberg David, Russo Mariano, Houser Kenneth, Crist Henry, Derr Jonathan B, Walter Vonn, Warrick Joshua I, Sheldon Kathryn E, Broach James, Bann Darrin V
Department of Surgery, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U.S.A.
Department of Biochemistry and Molecular Biology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U.S.A.
Laryngoscope. 2017 Jul;127 Suppl 3:S1-S9. doi: 10.1002/lary.26687. Epub 2017 May 29.
OBJECTIVES/HYPOTHESIS: In 1979, Three Mile Island (TMI) nuclear power plant experienced a partial meltdown with release of radioactive material. The effects of the accident on thyroid cancer (TC) in the surrounding population remain unclear. Radiation-induced TCs have a lower incidence of single nucleotide oncogenic driver mutations and higher incidence of gene fusions. We used next generation sequencing (NGS) to identify molecular signatures of radiation-induced TC in a cohort of TC patients residing near TMI during the time of the accident.
Case series.
We identified 44 patients who developed papillary thyroid carcinoma between 1974 and 2014. Patients who developed TC between 1984 and 1996 were at risk for radiation-induced TC, patients who developed TC before 1984 or after 1996 were the control group. We used targeted NGS of paired tumor and normal tissue from each patient to identify single nucleotide oncogenic driver mutations. Oncogenic gene fusions were identified using quantitative reverse transcription polymerase chain reaction.
We identified 15 patients in the at-risk group and 29 patients in the control group. BRAF mutations were identified in 53% patients in the at-risk group and 83% patients in the control group. The proportion of patients with BRAF mutations in the at-risk group was significantly lower than predicted by the The Cancer Genome Atlas cohort. Gene fusion or somatic copy number alteration drivers were identified in 33% tumors in the at-risk group and 14% of tumors in the control group.
Findings were consistent with observations from other radiation-exposed populations. These data raise the possibility that radiation released from TMI may have altered the molecular profile of TC in the population surrounding TMI.
4 Laryngoscope, 127:S1-S9, 2017.
目的/假设：1979年，三里岛（TMI）核电站发生部分堆芯熔毁并释放出放射性物质。此次事故对周边人群甲状腺癌（TC）的影响仍不明确。辐射诱发的甲状腺癌单核苷酸致癌驱动突变发生率较低，基因融合发生率较高。我们使用下一代测序（NGS）技术，在事故发生时居住在TMI附近的一组甲状腺癌患者中识别辐射诱发甲状腺癌的分子特征。
病例系列研究。
我们确定了44例在1974年至2014年间患乳头状甲状腺癌的患者。1984年至1996年间患甲状腺癌的患者有辐射诱发甲状腺癌的风险，1984年之前或1996年之后患甲状腺癌的患者为对照组。我们对每位患者的配对肿瘤组织和正常组织进行靶向NGS，以识别单核苷酸致癌驱动突变。使用定量逆转录聚合酶链反应鉴定致癌基因融合。
我们在风险组中确定了15例患者，在对照组中确定了29例患者。风险组中53%的患者和对照组中83%的患者检测到BRAF突变。风险组中BRAF突变患者的比例显著低于癌症基因组图谱队列预测的比例。在风险组33%的肿瘤和对照组14%的肿瘤中鉴定出基因融合或体细胞拷贝数改变驱动因素。
研究结果与其他受辐射人群的观察结果一致。这些数据增加了TMI释放的辐射可能改变TMI周边人群甲状腺癌分子特征的可能性。
4 喉镜，127:S1 - S9，2017年。
