Mutational load in carotid body tumor.

Autor: Kudryavtseva AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. rhizamoeba@mail.ru., Lukyanova EN; 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., Zaretsky AR; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 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., 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.; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia., Pavlov VS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Kobelyatskaya AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Melnikova NV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Dmitriev AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Polyakov AP; National Medical Research Radiological Center, Ministry of Health of the Russian Federation, 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., Krasnov GS; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia., Snezhkina AV; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2019 Mar 13; Vol. 12 (Suppl 2), pp. 39. Date of Electronic Publication: 2019 Mar 13.
DOI: 10.1186/s12920-019-0483-x
Abstrakt: Background: Carotid body tumor (CBT) is a rare neoplasm arising from paraganglion located near the bifurcation of the carotid artery. There is great intra-tumor heterogeneity, and CBT development could be associated with both germline and somatic allelic variants. Studies on the molecular genetics of CBT are limited, and the molecular mechanisms of its pathogenesis are not fully understood. This work is focused on the estimation of mutational load (ML) in CBT.
Methods: Using the NextSeq 500 platform, we performed exome sequencing of tumors with matched lymph node tissues and peripheral blood obtained from six patients with CBT. To obtain reliable results in tumors with low ML, we developed and successfully applied a complex approach for the analysis of sequencing data. ML was evaluated as the number of somatic variants per megabase (Mb) of the target regions covered by the Illumina TruSeq Exome Library Prep Kit.
Results: The ML in CBT varied in the range of 0.09-0.28/Mb. Additionally, we identified several pathogenic/likely pathogenic somatic and germline allelic variants across six patients studied (including TP53 variants).
Conclusions: Using the developed approach, we estimated the ML in CBT, which is much lower than in common malignant tumors. Identified variants in known paraganglioma/pheochromocytoma-causative genes and novel genes could be associated with the pathogenesis of CBT. The obtained results expand our knowledge of the mutation process in CBT as well as the biology of tumor development.
Databáze: MEDLINE
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