Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing.
Preliminary study on the molecular features of mutation in multiple primary oral cancer by whole exome sequencing.
复制标题
全外显子组测序初步研究多原发性口腔癌突变分子特征
DOI：
10.3389/fonc.2022.971546
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发表时间：
2022
影响因子：
4.7
通讯作者：
Liang, Yujie
中科院分区：
文献类型：
--
作者：
Li, Kan;Gong, Jianbin;Zheng, Qiuhan;Yang, Le;Mei, Xueying;Chen, Jianghai;Liao, Guiqing;Liang, Yujie
关键词：
多原发性癌症（MPC）是指在同一个体中同时或异时发生的癌症。近年来，随着恶性肿瘤患者生存时间的大大延长，MPC的发病率有所增加。仅从临床表现很难将MPC与同一解剖部位的原发癌（PC）区分开来。然而，它们的生物学行为似乎不同。在这项研究中，我们发现多原发性口腔癌（MP-OCs）的预后比原发性口腔癌（P-OCs）差。为了更好地了解MP-OC的分子机制，我们使用全外显子组测序（WES）分析了9例MP-OC和21例P-OC患者的样本。我们发现MP-OC比P-OC有更多的体细胞突变。MP-OC具有更复杂的突变特征，其与年龄相关和载脂蛋白B mRNA编辑催化多肽样（APOBEC）活性相关特征相关。与P-OC相比，MP-OC的肿瘤突变负荷（TMB）和突变等位基因肿瘤异质性（MATH）倾向于更高。KEGG和GO分析显示MP-OC与P-OC的不同途径。此外，MP-OC以扩增而非丢失作为拷贝数变异（CNV）的主要模式，而P-OC两者兼有。最后，我们没有发现明显不同的突变生殖系基因，但MSH-6突变可能是一个潜在的MP-OC驱动程序。总之，我们的初步结果表明，MP-OC和P-OC具有不同的分子特征。
Multiple primary cancers (MPCs) refer to cancers that occur simultaneously or metachronously in the same individual. The incidence of MPC has increased recently, as the survival time of malignant tumor patients has been greatly prolonged. It is difficult to differentiate MPC from primary cancers (PCs) in the same anatomical region from the clinical manifestation alone. However, their biological behaviors appear to be distinct. In this study, we show that the prognosis of multiple primary oral cancers (MP-OCs) is worse than primary oral cancers (P-OCs). To better understand the molecular mechanisms of MP-OC, we used whole exome sequencing (WES) to analyze samples from 9 patients with MP-OC and 21 patients with P-OC. We found more somatic mutations in MP-OC than in P-OC. MP-OC had more complicated mutation signatures, which were associated with age-related and Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) activity-related signatures. Tumor mutational burden (TMB) and mutant-allele tumor heterogeneity (MATH) of MP-OC trended higher compared to P-OC. KEGG and GO analysis showed the differential pathways of MP-OC versus P-OC. In addition, MP-OC took amplification, not loss, as the main pattern of copy number variation (CNV), while P-OC took both. Lastly, we did not find significantly different mutant germline genes, but MSH-6 mutation may be a potential MP-OC driver. In short, our preliminary results show that MP-OC and P-OC have different molecular characteristics.
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影响因子：
4.6
作者：
Bonneville R;Krook MA;Kautto EA;Miya J;Wing MR;Chen HZ;Reeser JW;Yu L;Roychowdhury S
通讯作者：
Roychowdhury S
影响因子：
10
作者：
Barclay, Matthew E.;Lyratzopoulos, Georgios;Rintoul, Robert C.
通讯作者：
Rintoul, Robert C.
影响因子：
7
作者：
Gillison, Maura L.;Akagi, Keiko;Symer, David E.
通讯作者：
Symer, David E.
影响因子：
4.5
作者：
Hong J;Gresham D
通讯作者：
Gresham D
影响因子：
2.8
作者：
Arlt, Martin F.;Rajendran, Sountharia;Birkeland, Shanda R.;Wilson, Thomas E.;Glover, Thomas W.
通讯作者：
Glover, Thomas W.