Ya Hu1, Xiang Zhang1, Ou Wang2, Xiaoping Xing2, Ming Cui1, Mengyi Wang1, Chengli Song3, Quan Liao4. 1. Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. 2. Department of Endocrinology, Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. 3. Novogene Bioinformatics Institute, Beijing, China. 4. Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. lqpumc@126.com.
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.
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.
Authors: Anton M F Kalsbeek; Eva K F Chan; Judith Grogan; Desiree C Petersen; Weerachai Jaratlerdsiri; Ruta Gupta; Ruth J Lyons; Anne-Maree Haynes; Lisa G Horvath; James G Kench; Phillip D Stricker; Vanessa M Hayes Journal: Prostate Date: 2017-11-14 Impact factor: 4.104
Authors: Elliot A Asare; Cord Sturgeon; David J Winchester; Lei Liu; Bryan Palis; Nancy D Perrier; Douglas B Evans; David P Winchester; Tracy S Wang Journal: Ann Surg Oncol Date: 2015-06-16 Impact factor: 5.344
Authors: Julia F Hopkins; Robert E Denroche; Jennifer A Aguiar; Faiyaz Notta; Ashton A Connor; Julie M Wilson; Lincoln D Stein; Steven Gallinger; Paul C Boutros Journal: Gastroenterology Date: 2018-03-29 Impact factor: 22.682
Authors: Siarhei A Dabravolski; Nikita G Nikiforov; Alexander D Zhuravlev; Nikolay A Orekhov; Liudmila M Mikhaleva; Alexander N Orekhov Journal: Int J Mol Sci Date: 2021-12-31 Impact factor: 5.923