{"title":"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","authors":"Shanshan Shi, Yuxi Gong, Xiao Li, Ying Ding, Guoxin Song, Haiyan Liu, Zhihong Zhang","doi":"10.1089/gtmb.2022.0118","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Aims:</i></b> 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. <b><i>Materials and Methods:</i></b> 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 <i>in situ</i> hybridization and immunohistochemistry were used to validate the NGS findings. <b><i>Result:</i></b> 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 <i>RAS-RAF</i> pathway and 18 cases (72%) with mutations in the <i>PI3K</i> pathway among the MSI-H CRCs. The remaining two cases included an EMAP Like 4-ALK Receptor Tyrosine Kinase (<i>EML4-ALK)</i> fusion and one with a Erb-B2 Receptor Tyrosine Kinase 2 (<i>ERBB2)</i> missense mutation. <b><i>Conclusion:</i></b> 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.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Mutations in Classical Signaling Pathways and Their Functional Impact in Microsatellite Instability High Colorectal Cancer.\",\"authors\":\"Shanshan Shi, Yuxi Gong, Xiao Li, Ying Ding, Guoxin Song, Haiyan Liu, Zhihong Zhang\",\"doi\":\"10.1089/gtmb.2022.0118\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Aims:</i></b> 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. <b><i>Materials and Methods:</i></b> 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 <i>in situ</i> hybridization and immunohistochemistry were used to validate the NGS findings. <b><i>Result:</i></b> 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 <i>RAS-RAF</i> pathway and 18 cases (72%) with mutations in the <i>PI3K</i> pathway among the MSI-H CRCs. The remaining two cases included an EMAP Like 4-ALK Receptor Tyrosine Kinase (<i>EML4-ALK)</i> fusion and one with a Erb-B2 Receptor Tyrosine Kinase 2 (<i>ERBB2)</i> missense mutation. <b><i>Conclusion:</i></b> 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.</p>\",\"PeriodicalId\":12603,\"journal\":{\"name\":\"Genetic testing and molecular biomarkers\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetic testing and molecular biomarkers\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/gtmb.2022.0118\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetic testing and molecular biomarkers","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/gtmb.2022.0118","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.
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