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Targeted next-generation sequencing in papillary thyroid carcinoma patients looking for germline variants predisposing to the disease

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Abstract

Purposess

The purpose of this study was using next-generation sequencing technique to explore the potential association between germline variants of 14 targeted genes and papillary thyroid carcinoma (PTC) predisposition as well as disease progression.

Methods

In all, 516 subjects were enrolled in this study including 416 PTC patients and 100 healthy controls. PTC patients were divided into distant metastasis group and non-distant metastasis group. Patients in distant metastasis group were further divided into radioiodine-refractory PTC (RR-PTC) and non-RR-PTC depending on their response to radioiodine therapy. Genomic DNA was extracted from peripheral blood sample and MiSeq Benchtop Sequencer was used for sequencing.

Results

We found rs11246050 in NLRP6 (dominant model, OR/95% CI: 2.028/1.091–3.769, p = 0.025), rs2286742 and rs3740530 in HABP2 (recessive model, OR/95% CI: 9.644/1.307–71.16, p = 0.026 and 3.989/1.413–11.26, p = 0.009), rs2736098 in TERT (recessive model, OR/95% CI: 2.322/1.028–5.242. p = 0.042) and rs62054619 in GAS8-AS1 (recessive model, OR/95% CI: 2.219/1.067–4.617, p = 0.033) were associated with the risk of PTC. rs1137282 in KRAS (dominant model, OR/95% CI: 0.5430/0.3192–0.9236, p = 0.024), rs1347591 and rs4461062 in NUP93 (dominant model, OR/95% CI: 0.6121/0.4128–0.9076, p = 0.015 and 0.6156/0.4157–0.9117, p = 0.015) were associated with low risk of distant metastatic disease in PTC patients. rs33954691 in TERT was associated with the risk of RR-PTC under dominant model (OR/95% CI: 3.161/1.596–6.262).

Conclusions

Germline variants of related genes could be associated with the susceptibility of PTC as well as disease progression (distant metastasis and radioiodine-refractory status). However, these results must be further verified and the potential biological functions of these germline variants in the pathogenesis of PTC remain to be determined in future studies.

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Acknowledgements

The authors thank Genesky Bio-Tech Co., Ltd. for their help with gene sequencing and analysis.

Funding

This work was supported by Shanghai key discipline of medical imaging (no. 2017ZZ02005) and the National Natural Science Foundation of China (no. 81771865).

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  1. These authors contributed equally: Chen-Tian Shen, Guo-Qiang Zhang

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  1. Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 200233, Shanghai, People’s Republic of China

    Chen-Tian Shen, Guo-Qiang Zhang, Zhong-Ling Qiu, Hong-Jun Song, Zhen-Kui Sun & Quan-Yong Luo

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Shen, CT., Zhang, GQ., Qiu, ZL. et al. Targeted next-generation sequencing in papillary thyroid carcinoma patients looking for germline variants predisposing to the disease. Endocrine 64, 622–631 (2019). https://doi.org/10.1007/s12020-019-01878-0

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