Next-generation sequencing identifies novel mitochondrial variants in pituitary adenomas
| العنوان: | Next-generation sequencing identifies novel mitochondrial variants in pituitary adenomas |
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| المؤلفون: | Lilla Reiniger, Sándor Czirják, Krisztina Németh, Nikolette Szücs, Lilla Krokker, Attila Patocs, Boglárka Szabó, Henriett Butz, Otto Darvasi, Petra Anna Kurucz, István Likó, Peter Igaz |
| المصدر: | Journal of Endocrinological Investigation |
| بيانات النشر: | Springer International Publishing, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Genetic variations, Adenoma, Adult, Male, Mitochondrial DNA, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Pathogenesis, Biology, Genome, DNA, Mitochondrial, DNA sequencing, 03 medical and health sciences, symbols.namesake, Young Adult, 0302 clinical medicine, Endocrinology, Pituitary adenoma, medicine, Humans, Pituitary Neoplasms, Aged, Genetics, Sanger sequencing, Aged, 80 and over, Genetic Variation, High-Throughput Nucleotide Sequencing, Middle Aged, medicine.disease, Prognosis, Heteroplasmy, Mitochondria, 030220 oncology & carcinogenesis, Genome, Mitochondrial, symbols, Next-generation sequencing, Cambridge Reference Sequence, Original Article, Female, Biomarkers, Follow-Up Studies |
| الوصف: | Purpose Disrupted mitochondrial functions and genetic variants of mitochondrial DNA (mtDNA) have been observed in different human neoplasms. Next-generation sequencing (NGS) can be used to detect even low heteroplasmy-level mtDNA variants. We aimed to investigate the mitochondrial genome in pituitary adenomas by NGS. Methods We analysed 11 growth hormone producing and 33 non-functioning [22 gonadotroph and 11 hormone immunonegative] pituitary adenomas using VariantPro™ Mitochondrion Panel on Illumina MiSeq instrument. Revised Cambridge Reference Sequence (rCRS) of the mtDNA was used as reference. Heteroplasmy was determined using a 3% cutoff. Results 496 variants were identified in pituitary adenomas with overall low level of heteroplasmy (7.22%). On average, 35 variants were detected per sample. Samples harbouring the highest number of variants had the highest Ki-67 indices independently of histological subtypes. We identified eight variants (A11251G, T4216C, T16126C, C15452A, T14798C, A188G, G185A, and T16093C) with different prevalences among different histological groups. T16189C was found in 40% of non-recurrent adenomas, while it was not present in the recurrent ones. T14798C and T4216C were confirmed by Sanger sequencing in all 44 samples. 100% concordance was found between NGS and Sanger method. Conclusions NGS is a reliable method for investigating mitochondrial genome and heteroplasmy in pituitary adenomas. Out of the 496 detected variants, 414 have not been previously reported in pituitary adenoma. The high number of mtDNA variants may contribute to adenoma genesis, and some variants (i.e., T16189C) might associate with benign behaviour. Electronic supplementary material The online version of this article (10.1007/s40618-019-1005-6) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1720-8386 0391-4097 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7917d841709888f1f6612fbe85e1fd19Test http://europepmc.org/articles/PMC6647476Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7917d841709888f1f6612fbe85e1fd19 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17208386 03914097 |
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