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Laryngoscope. 2017 Jul;127 Suppl 3:S1-S9. doi: 10.1002/lary.26687. Epub 2017 May 29.

Altered molecular profile in thyroid cancers from patients affected by the Three Mile Island nuclear accident.

Author information

1
Department of Surgery, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U.S.A.
2
Department of Biochemistry and Molecular Biology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U.S.A.
3
Department of Pathology, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U.S.A.
4
Institute for Personalized Medicine, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U.S.A.
5
Department of Biochemistry and Public Health Sciences, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania, U.S.A.

Abstract

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.

STUDY DESIGN:

Case series.

METHODS:

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.

RESULTS:

We identified 15 patients in the at-risk group and 29 patients in the control group. BRAFV600E 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.

CONCLUSIONS:

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.

LEVEL OF EVIDENCE:

4 Laryngoscope, 127:S1-S9, 2017.

KEYWORDS:

Papillary thyroid cancer; Three Mile Island; next-generation sequencing; radiation

PMID:
28555940
DOI:
10.1002/lary.26687
[Indexed for MEDLINE]

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