颈动脉体瘤的外显子组分析
Exome analysis of carotid body tumor.
作者信息
Snezhkina Anastasiya V, Lukyanova Elena N, Kalinin Dmitry V, Pokrovsky Anatoly V, Dmitriev Alexey A, Koroban Nadezhda V, Pudova Elena A, Fedorova Maria S, Volchenko Nadezhda N, Stepanov Oleg A, Zhevelyuk Ekaterina A, Kharitonov Sergey L, Lipatova Anastasiya V, Abramov Ivan S, Golovyuk Alexander V, Yegorov Yegor E, Vishnyakova Khava S, Moskalev Alexey A, Krasnov George S, Melnikova Nataliya V, Shcherbo Dmitry S, Kiseleva Marina V, Kaprin Andrey D, Alekseev Boris Y, Zaretsky Andrew R, Kudryavtseva Anna V
机构信息
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Vishnevsky Institute of Surgery, Ministry of Health of the Russian Federation, Moscow, Russia.
出版信息
BMC Med Genomics. 2018 Feb 13;11(Suppl 1):17. doi: 10.1186/s12920-018-0327-0.
BACKGROUND
Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Paragangliomas are commonly associated with germline and somatic mutations involving at least one of more than thirty causative genes. However, the specific functionality of a number of these genes involved in the formation of paragangliomas has not yet been fully investigated.
METHODS
Exome library preparation was carried out using Nextera® Rapid Capture Exome Kit (Illumina, USA). Sequencing was performed on NextSeq 500 System (Illumina).
RESULTS
Exome analysis of 52 CBTs revealed potential driver mutations (PDMs) in 21 genes: ARNT, BAP1, BRAF, BRCA1, BRCA2, CDKN2A, CSDE1, FGFR3, IDH1, KIF1B, KMT2D, MEN1, RET, SDHA, SDHB, SDHC, SDHD, SETD2, TP53BP1, TP53BP2, and TP53I13. In many samples, more than one PDM was identified. There are also 41% of samples in which we did not identify any PDM; in these cases, the formation of CBT was probably caused by the cumulative effect of several not highly pathogenic mutations. Estimation of average mutation load demonstrated 6-8 mutations per megabase (Mb). Genes with the highest mutation rate were identified.
CONCLUSIONS
Exome analysis of 52 CBTs for the first time revealed the average mutation load for these tumors and also identified potential driver mutations as well as their frequencies and co-occurrence with the other PDMs.
背景
颈动脉体瘤（CBT）是头颈部副神经节瘤（HNPGLs）的一种形式，起源于颈动脉分叉处。副神经节瘤通常与涉及三十多个致病基因中至少一个的种系和体细胞突变相关。然而，这些参与副神经节瘤形成的许多基因的具体功能尚未得到充分研究。
方法
使用Nextera®快速捕获外显子试剂盒（美国Illumina公司）进行外显子文库制备。在NextSeq 500系统（Illumina）上进行测序。
结果
对52例CBT进行外显子分析，发现21个基因存在潜在驱动突变（PDM）：ARNT、BAP1、BRAF、BRCA1、BRCA2、CDKN2A、CSDE1、FGFR3、IDH1、KIF1B、KMT2D、MEN1、RET、SDHA、SDHB、SDHC、SDHD、SETD2、TP53BP1、TP53BP2和TP53I13。在许多样本中，鉴定出不止一个PDM。还有41%的样本未鉴定出任何PDM；在这些情况下，CBT的形成可能是由几个致病性不高的突变的累积效应引起的。平均突变负荷估计为每兆碱基（Mb）6 - 8个突变。确定了突变率最高的基因。
结论
对52例CBT进行外显子分析首次揭示了这些肿瘤的平均突变负荷，还鉴定了潜在驱动突变及其频率以及与其他PDM的共现情况。
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