Novel potential causative genes in carotid paragangliomas.

Autor: Snezhkina AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Lukyanova EN; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Zaretsky AR; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kalinin DV; Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia., Pokrovsky AV; Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia., Golovyuk AL; Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia., Krasnov GS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Fedorova MS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Pudova EA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kharitonov SL; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Melnikova NV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Alekseev BY; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Kiseleva MV; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Kaprin AD; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Dmitriev AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kudryavtseva AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. rhizamoeba@mail.ru.
Jazyk: angličtina
Zdroj: BMC medical genetics [BMC Med Genet] 2019 Apr 09; Vol. 20 (Suppl 1), pp. 48. Date of Electronic Publication: 2019 Apr 09.
DOI: 10.1186/s12881-019-0770-6
Abstrakt: Background: Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from the paraganglion at the bifurcation of the carotid artery and are responsible for approximately 65% of all head and neck paragangliomas. CPGLs can occur sporadically or along with different hereditary tumor syndromes. Approximately 30 genes are known to be associated with CPGLs. However, the genetic basis behind the development of these tumors is not fully elucidated, and the molecular mechanisms underlying CPGL pathogenesis remain unclear.
Methods: Whole exome and transcriptome high-throughput sequencing of CPGLs was performed on an Illumina platform. Exome libraries were prepared using a Nextera Rapid Capture Exome Kit (Illumina) and were sequenced under 75 bp paired-end model. For cDNA library preparation, a TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold (Illumina) was used; transcriptome sequencing was carried out with 100 bp paired-end read length. Obtained data were analyzed using xseq which estimates the influence of mutations on gene expression profiles allowing to identify potential causative genes.
Results: We identified a total of 16 candidate genes (MYH15, CSP1, MYH3, PTGES3L, CSGALNACT2, NMD3, IFI44, GMCL1, LSP1, PPFIBP2, RBL2, MAGED1, CNIH3, STRA6, SLC6A13, and ATM) whose variants potentially influence their expression (cis-effect). The strongest cis-effect of loss-of-function variants was found in MYH15, CSP1, and MYH3, and several likely pathogenic variants in these genes associated with CPGLs were predicted.
Conclusions: Using the xseq probabilistic model, three novel potential causative genes, namely MYH15, CSP1, and MYH3, were identified in carotid paragangliomas.
Databáze: MEDLINE
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