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Endocrine

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22.07.2021 | Original Article

Spectrum of mitochondrial genomic variation in parathyroid neoplasms

verfasst von: Ya Hu, Xiang Zhang, Ou Wang, Xiaoping Xing, Ming Cui, Mengyi Wang, Chengli Song, Quan Liao

Erschienen in: Endocrine | Ausgabe 3/2021

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Abstract

Purpose

Mitochondrial DNA (mtDNA) variations have been implicated in various cancer types. Several attempts have been made in benign parathyroid adenoma (PA); however, mtDNA variants and copy number alterations have not been investigated in parathyroid carcinoma (PC). The present study aimed to explore the variations in the mitochondrial genome in parathyroid neoplasms.

Methods

In this study, ultradeep targeted sequencing of mtDNA was performed in 12 cases with PC and 25 cases with PA. Germline and somatic variants in the mitochondrial genome were analysed according to clinical features. The mtDNA copy number relative to nuclear DNA was measured.

Results

A total of 821 germline variants and 23 somatic mutations were identified. All 160 germline nonsynonymous variants in the coding sequence (CDS) were predicted to be likely benign, and germline variants frequently occurred (26.3%) in the displacement loop region. Tumour somatic mutation in a CDS with heteroplasmic factor (HF) >0.8 showed a higher mtDNA copy number (p = 0.039). Using Spearman’s rank test, tumour mtDNA copy number revealed a positive correlation with serum levels of intact parathyroid hormone and calcium.

Conclusion

Our results demonstrate that null recurrent mtDNA mutational hotspots were PC specific. An increased mtDNA copy number in parathyroid neoplasms was associated with somatic CDS mutations with a high HF and major clinical features. Larger cohort investigations should be performed in future analyses.

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Titel: Spectrum of mitochondrial genomic variation in parathyroid neoplasms
verfasst von: Ya Hu
Xiang Zhang
Ou Wang
Xiaoping Xing
Ming Cui
Mengyi Wang
Chengli Song
Quan Liao
Publikationsdatum: 22.07.2021
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 3/2021
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-021-02825-8

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Spectrum of mitochondrial genomic variation in parathyroid neoplasms

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