微卫星不稳定性高结直肠癌经典信号通路突变及其功能影响

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Genetic testing and molecular biomarkers Pub Date : 2023-03-01 DOI:10.1089/gtmb.2022.0118
Shanshan Shi, Yuxi Gong, Xiao Li, Ying Ding, Guoxin Song, Haiyan Liu, Zhihong Zhang
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引用次数: 1

摘要

目的:微卫星不稳定性高结直肠癌(MSI-H)是结直肠癌(crc)中一个独特的群体。本研究探讨了MSI-H型结直肠癌中常见信号通路基因的突变及其潜在的临床意义。材料与方法:从384例原发性crc中选取25例MSI-H肿瘤,并从病历中收集相关临床病理资料。使用商业试剂盒使用下一代测序(NGS)检测这些肿瘤中关键癌基因的突变状态。采用荧光原位杂交和免疫组织化学方法验证NGS结果。结果:本研究中MSI-H病例占原发性crc的6.51%,具有特殊的临床病理特征。NGS显示,每个肿瘤中评估的靶基因的平均突变数为3.36,范围为1至9。总的来说,MSI-H crc中有17例(68%)RAS-RAF通路突变,18例(72%)PI3K通路突变。其余2例包括EMAP样4-ALK受体酪氨酸激酶(EML4-ALK)融合和erbb - b2受体酪氨酸激酶2 (ERBB2)错义突变。结论:本研究发现MSI-H crc中不同信号通路中的多种变异相互存在,表明这种异质性肿瘤组需要复杂的治疗反应。因此,建议对此类患者(如NGS)进行额外的临床分子检测,以告知适当的治疗策略。
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Mutations in Classical Signaling Pathways and Their Functional Impact in Microsatellite Instability High Colorectal Cancer.

Aims: Colorectal carcinomas with microsatellite instability high (MSI-H) are a distinctive group among colorectal cancers (CRCs). This study investigated the mutations of genes in the common signaling pathways and their potential clinical implications in MSI-H CRC. Materials and Methods: Twenty-five MSI-H tumors were selected from 384 primary CRCs, and the related clinical and pathological information were also collected from medical records. A commercial kit was used to detect the mutational status of crucial oncogenes within these tumors using next generation sequencing (NGS). Fluorescence in situ hybridization and immunohistochemistry were used to validate the NGS findings. Result: In the present study, MSI-H cases accounted for 6.51% of primary CRCs, with special clinicopathological features. NGS showed that the average number of mutations per tumor in the target genes evaluated was 3.36 and ranged from 1 to 9. In total, there were 17 cases (68%) with mutations in the RAS-RAF pathway and 18 cases (72%) with mutations in the PI3K pathway among the MSI-H CRCs. The remaining two cases included an EMAP Like 4-ALK Receptor Tyrosine Kinase (EML4-ALK) fusion and one with a Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) missense mutation. Conclusion: This study found multiple variants within different signaling pathways that were mutually present in MSI-H CRCs, suggesting that such a heterogeneous group of tumors requires complex treatment responses. Thus, additional clinical molecular testing is recommended for such patients, such as NGS, to inform the appropriate treatment strategies.

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来源期刊
CiteScore
2.50
自引率
7.10%
发文量
63
审稿时长
1 months
期刊介绍: Genetic Testing and Molecular Biomarkers is the leading peer-reviewed journal covering all aspects of human genetic testing including molecular biomarkers. The Journal provides a forum for the development of new technology; the application of testing to decision making in an increasingly varied set of clinical situations; ethical, legal, social, and economic aspects of genetic testing; and issues concerning effective genetic counseling. This is the definitive resource for researchers, clinicians, and scientists who develop, perform, and interpret genetic tests and their results. Genetic Testing and Molecular Biomarkers coverage includes: -Diagnosis across the life span- Risk assessment- Carrier detection in individuals, couples, and populations- Novel methods and new instrumentation for genetic testing- Results of molecular, biochemical, and cytogenetic testing- Genetic counseling
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