通过二代测序对全内脏反位的结直肠癌进行综合分子谱分析

Comprehensive Molecular Profiling of Colorectal Cancer With Situs Inversus Totalis by Next-Generation Sequencing.

作者信息

Li Hongsen, Gong Liu, Cheng Huanqing, Wang Huina, Zhang Xiaochen, Rao Chuangzhou, Song Zhangfa, Wang Da, Lou Haizhou, Lou Feng, Cao Shanbo, Pan Hongming, Fang Yong

机构信息

Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Prenatal Diagnosis Center, Affiliated Hospital of Weifang Medical University, Weifang, China.

出版信息

Front Oncol. 2022 Apr 20;12:813253. doi: 10.3389/fonc.2022.813253. eCollection 2022.

DOI:10.3389/fonc.2022.813253

PMID:35530355

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9067615/

Abstract

BACKGROUND

Colorectal cancer (CRC) is one of the most prevalent malignances worldwide. However, CRC with situs inversus totalis (SCRC) is extremely rare, and molecular characterization of this disease has never been investigated.

METHODS

Tumor tissue samples from 8 patients with SCRC and 33 CRC patients without situs inversus totalis (NSCRC) were subjected to multigene next-generation sequencing.

RESULTS

The most frequently mutated genes in SCRC were , , , , , , and . A high frequency of SCRC tumors had mutations in DNA damage repair genes. Single amino acid substitutions in the DNA damage repair genes caused by continuous double base substitution was identified in the majority of this population. Furthermore, mutational profiles showed notable differences between the SCRC and NSCRC groups. In particular, , , , , , , , and mutations were more frequently observed in SCRC patients. The mutation loci distributions of in the SCRC cohort differed from that of the NSCRC cohort. Additionally, differences in the targeted genomic profiles and base substitution patterns were observed between the two groups.

CONCLUSIONS

These findings comprehensively revealed a molecular characterization of SCRC, which will contribute to the development of personalized therapy and improved clinical management of SCRC patients.

摘要

背景

结直肠癌（CRC）是全球最常见的恶性肿瘤之一。然而，全内脏反位的结直肠癌（SCRC）极为罕见，且尚未对该疾病的分子特征进行研究。

方法

对8例SCRC患者和33例无全内脏反位的CRC患者（NSCRC）的肿瘤组织样本进行多基因二代测序。

结果

SCRC中最常发生突变的基因是、、、、、和。SCRC肿瘤中DNA损伤修复基因发生突变的频率较高。在该人群的大多数个体中，鉴定出由连续双碱基替换导致的DNA损伤修复基因中的单氨基酸替换。此外，SCRC组和NSCRC组的突变谱存在显著差异。特别是，、、、、、、和突变在SCRC患者中更频繁地被观察到。SCRC队列中的突变位点分布与NSCRC队列不同。此外，两组之间在靶向基因组图谱和碱基替换模式上也存在差异。