• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

通过靶向测序对杜克B期和C期结直肠癌体细胞改变进行分子特征分析

Molecular Characterization of Somatic Alterations in Dukes' B and C Colorectal Cancers by Targeted Sequencing.

作者信息

Abdul Shafina-Nadiawati, Ab Mutalib Nurul-Syakima, Sean Khor S, Syafruddin Saiful E, Ishak Muhiddin, Sagap Ismail, Mazlan Luqman, Rose Isa M, Abu Nadiah, Mokhtar Norfilza M, Jamal Rahman

机构信息

UKM Medical Molecular Biology InstituteUniversiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Thermo Fisher ScientificShah Alam, Malaysia.

出版信息

Front Pharmacol. 2017 Jul 18;8:465. doi: 10.3389/fphar.2017.00465. eCollection 2017.

DOI:10.3389/fphar.2017.00465
PMID:28769798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5513919/
Abstract

Despite global progress in research, improved screening and refined treatment strategies, colorectal cancer (CRC) remains as the third most common malignancy. As each type of cancer is different and exhibits unique alteration patterns, identifying and characterizing gene alterations in CRC that may serve as biomarkers might help to improve diagnosis, prognosis and predict potential response to therapy. With the emergence of next generation sequencing technologies (NGS), it is now possible to extensively and rapidly identify the gene profile of individual tumors. In this study, we aimed to identify actionable somatic alterations in Dukes' B and C in CRC via NGS. Targeted sequencing of 409 cancer-related genes using the Ion Ampliseq Comprehensive Cancer Panel was performed on genomic DNA obtained from paired fresh frozen tissues, cancer and normal, of Dukes' B ( = 10) and Dukes' C ( = 9) CRC. The sequencing results were analyzed using Torrent Suite, annotated using ANNOVAR and validated using Sanger sequencing. A total of 141 somatic non-synonymous sequence variations were identified in 86 genes. Among these, 64 variants (45%) were predicted to be deleterious, 38 variants (27%) possibly deleterious while the other 39 variants (28%) have low or neutral protein impact. Seventeen genes have alterations with frequencies of ≥10% in the patient cohort and with 14 overlapped genes in both Dukes' B and C. The adenomatous polyposis coli gene (APC) was the most frequently altered gene in both groups ( = 6 in Dukes' B and C). In addition, was more frequently altered in Dukes' C ( = 7) compared to Dukes' B ( = 4). Ten variants in , namely p.R283, p.N778fs, p.R805, p.Y935fs, p.E941fs, p.E1057, p.I1401fs, p.Q1378, p.E1379, and p.A1485fs were predicted to be driver variants. APC remains as the most frequently altered gene in the intermediate stages of CRC. Wnt signaling pathway is the major affected pathway followed by P53, RAS, TGF-β, and PI3K signaling. We reported the alteration profiles in each of the patient which has the potential to affect the clinical decision. We believe that this study will add further to the understanding of CRC molecular landscape.

摘要

尽管在研究、改进筛查和优化治疗策略方面取得了全球进展，但结直肠癌（CRC）仍然是第三大常见恶性肿瘤。由于每种癌症都不同且表现出独特的改变模式，识别和表征CRC中可能作为生物标志物的基因改变可能有助于改善诊断、预后并预测对治疗的潜在反应。随着下一代测序技术（NGS）的出现，现在有可能广泛且快速地识别个体肿瘤的基因图谱。在本研究中，我们旨在通过NGS识别CRC中Dukes' B和C期的可操作体细胞改变。使用Ion Ampliseq Comprehensive Cancer Panel对409个癌症相关基因进行靶向测序，该测序是在从Dukes' B期（n = 10）和Dukes' C期（n = 9）CRC的配对新鲜冷冻组织（癌组织和正常组织）中获得的基因组DNA上进行的。测序结果使用Torrent Suite进行分析，使用ANNOVAR进行注释，并使用Sanger测序进行验证。在86个基因中总共鉴定出141个体细胞非同义序列变异。其中，64个变异（45%）被预测为有害，38个变异（27%）可能有害，而其他39个变异（28%）对蛋白质的影响较低或为中性。17个基因在患者队列中的改变频率≥10%，且在Dukes' B和C期有14个重叠基因。腺瘤性息肉病大肠杆菌基因（APC）是两组中改变最频繁的基因（Dukes' B和C期均为6例）。此外，与Dukes' B期（4例）相比，Dukes' C期（7例）中[此处原文缺失基因名称]的改变更频繁。[此处原文缺失基因名称]中的10个变异，即p.R283、p.N778fs、p.R805、p.Y935fs、p.E941fs、p.E1057、p.I1401fs、p.Q1378、p.E1379和p.A1485fs被预测为驱动变异。APC仍然是CRC中间阶段改变最频繁的基因。Wnt信号通路是主要受影响的通路，其次是P53、RAS、TGF-β和PI3K信号通路。我们报告了每个患者的改变图谱，这些图谱有可能影响临床决策。我们相信这项研究将进一步加深对CRC分子格局的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/43b7757d039a/fphar-08-00465-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/436b90a6e360/fphar-08-00465-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/dda28fed933f/fphar-08-00465-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/bb25d2be2a9f/fphar-08-00465-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/768674da09ce/fphar-08-00465-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/ae6d61a54b36/fphar-08-00465-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/26dbb8bdf242/fphar-08-00465-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/7ec2d0aee931/fphar-08-00465-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/2e6a07b65002/fphar-08-00465-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/43b7757d039a/fphar-08-00465-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/436b90a6e360/fphar-08-00465-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/dda28fed933f/fphar-08-00465-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/bb25d2be2a9f/fphar-08-00465-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/768674da09ce/fphar-08-00465-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/ae6d61a54b36/fphar-08-00465-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/26dbb8bdf242/fphar-08-00465-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/7ec2d0aee931/fphar-08-00465-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/2e6a07b65002/fphar-08-00465-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c595/5513919/43b7757d039a/fphar-08-00465-g009.jpg

相似文献

1
Molecular Characterization of Somatic Alterations in Dukes' B and C Colorectal Cancers by Targeted Sequencing.通过靶向测序对杜克B期和C期结直肠癌体细胞改变进行分子特征分析
Front Pharmacol. 2017 Jul 18;8:465. doi: 10.3389/fphar.2017.00465. eCollection 2017.
2
Microsatellite instability-low colorectal cancer acquires a KRAS mutation during the progression from Dukes' A to Dukes' B.微卫星不稳定性低的结直肠癌在从杜克A期进展到杜克B期的过程中获得KRAS突变。
Carcinogenesis. 2009 Mar;30(3):494-9. doi: 10.1093/carcin/bgp017. Epub 2009 Jan 15.
3
Expression Pattern of PDE4B, PDE4D, and SFRP5 Markers in Colorectal Cancer.PDE4B、PDE4D 和 SFRP5 标志物在结直肠癌中的表达模式。
Medicina (Kaunas). 2024 Jul 25;60(8):1202. doi: 10.3390/medicina60081202.
4
Molecular detection of APC, K- ras, and p53 mutations in the serum of colorectal cancer patients as circulating biomarkers.作为循环生物标志物的结直肠癌患者血清中APC、K-ras和p53突变的分子检测
World J Surg. 2004 Jul;28(7):721-6. doi: 10.1007/s00268-004-7366-8. Epub 2004 Jun 8.
5
Influence of age on adenomatous polyposis coli and p53 mutation frequency in sporadic colorectal cancer-rarity of co-occurrence of mutations in APC, K-ras, and p53 genes.年龄对散发性结直肠癌中腺瘤性息肉病 coli 和 p53 突变频率的影响——APC、K-ras 和 p53 基因共突变的罕见性
Virchows Arch. 2004 Nov;445(5):465-71. doi: 10.1007/s00428-004-1116-z. Epub 2004 Sep 24.
6
Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience.多基因检测揭示埃及结直肠癌患者的癌症特异性和常见体细胞突变
Curr Issues Mol Biol. 2022 Mar 18;44(3):1332-1352. doi: 10.3390/cimb44030090.
7
Prognostic significance of PDCD4 expression and association with microRNA-21 in each Dukes' stage of colorectal cancer patients.PDCD4 表达的预后意义及其与结直肠癌各 Dukes 分期患者中 microRNA-21 的关系。
Oncol Rep. 2012 May;27(5):1384-92. doi: 10.3892/or.2012.1648. Epub 2012 Jan 19.
8
Clinical significance of microRNA-21 as a biomarker in each Dukes' stage of colorectal cancer.微小RNA-21作为生物标志物在结直肠癌各Dukes分期中的临床意义。
Oncol Rep. 2015 Feb;33(2):573-82. doi: 10.3892/or.2014.3614. Epub 2014 Nov 21.
9
Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes' stage B and C colorectal cancer.循环肿瘤细胞，包括肿瘤干细胞样细胞，在外周血中的临床意义与 Dukes'B 和 C 期结直肠癌患者的复发和预后相关。
J Clin Oncol. 2011 Apr 20;29(12):1547-55. doi: 10.1200/JCO.2010.30.5151. Epub 2011 Mar 21.
10
Microsatellite instability in sporadic-colon-cancer patients with and without liver metastases.伴有和不伴有肝转移的散发性结肠癌患者的微卫星不稳定性
Int J Cancer. 1997 Aug 22;74(4):470-4. doi: 10.1002/(sici)1097-0215(19970822)74:4<470::aid-ijc20>3.0.co;2-c.

引用本文的文献

1
Whole genome sequencing of Malaysian colorectal cancer patients reveals specific druggable somatic mutations.马来西亚结直肠癌患者的全基因组测序揭示了特定的可靶向治疗的体细胞突变。
Front Mol Biosci. 2023 Feb 14;9:997747. doi: 10.3389/fmolb.2022.997747. eCollection 2022.
2
Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer.溃疡性结肠炎、结直肠癌和结肠炎相关癌症中细胞因子诱导的 PI3K 相关基因的靶向测序。
Int J Mol Sci. 2022 Sep 29;23(19):11472. doi: 10.3390/ijms231911472.
3
Alteration in the Immune Microenvironment Based on APC Status in MSS/pMMR Colon Cancer.

本文引用的文献

1
Olaparib for the treatment of BRCA-mutated advanced ovarian cancer.奥拉帕利治疗 BRCA 突变型晚期卵巢癌。
Am J Health Syst Pharm. 2016 Jul 15;73(14):1037-41. doi: 10.2146/ajhp150550.
2
A multigene mutation classification of 468 colorectal cancers reveals a prognostic role for APC.468 例结直肠癌的多基因突变分类揭示 APC 的预后作用。
Nat Commun. 2016 Jun 15;7:11743. doi: 10.1038/ncomms11743.
3
Clinical significance of frequent somatic mutations detected by high-throughput targeted sequencing in archived colorectal cancer samples.
基于 APC 状态的 MSS/pMMR 结直肠癌免疫微环境的改变。
Dis Markers. 2022 Jul 27;2022:3592990. doi: 10.1155/2022/3592990. eCollection 2022.
4
Genome-Wide Open Chromatin Methylome Profiles in Colorectal Cancer.结直肠癌全基因组开放染色质甲基化组图谱。
Biomolecules. 2020 May 5;10(5):719. doi: 10.3390/biom10050719.
5
Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine.结直肠癌中较少突变基因的可操作性及其在精准医学中的作用。
Biomolecules. 2020 Mar 20;10(3):476. doi: 10.3390/biom10030476.
高通量靶向测序在存档结直肠癌样本中检测到的常见体细胞突变的临床意义
J Transl Med. 2016 May 4;14(1):118. doi: 10.1186/s12967-016-0878-9.
4
TP53, PIK3CA, FBXW7 and KRAS Mutations in Esophageal Cancer Identified by Targeted Sequencing.通过靶向测序鉴定食管癌中的TP53、PIK3CA、FBXW7和KRAS突变
Cancer Genomics Proteomics. 2016 May-Jun;13(3):231-8.
5
KDR Mutation as a Novel Predictive Biomarker of Exceptional Response to Regorafenib in Metastatic Colorectal Cancer.KDR突变作为转移性结直肠癌对瑞戈非尼产生特殊反应的新型预测生物标志物
Cureus. 2016 Feb 3;8(2):e478. doi: 10.7759/cureus.478.
6
Cancer statistics, 2016.癌症统计数据，2016 年。
CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. doi: 10.3322/caac.21332. Epub 2016 Jan 7.
7
DGIdb 2.0: mining clinically relevant drug-gene interactions.DGIdb 2.0：挖掘临床相关的药物-基因相互作用
Nucleic Acids Res. 2016 Jan 4;44(D1):D1036-44. doi: 10.1093/nar/gkv1165. Epub 2015 Nov 3.
8
KEGG as a reference resource for gene and protein annotation.KEGG作为基因和蛋白质注释的参考资源。
Nucleic Acids Res. 2016 Jan 4;44(D1):D457-62. doi: 10.1093/nar/gkv1070. Epub 2015 Oct 17.
9
Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases.KRAS G12V突变在841例接受手术切除的白种人肺腺癌病例中的预后价值。
Br J Cancer. 2015 Oct 20;113(8):1206-15. doi: 10.1038/bjc.2015.327. Epub 2015 Sep 15.
10
Genetic mutations in human rectal cancers detected by targeted sequencing.通过靶向测序检测到的人类直肠癌中的基因突变。
J Hum Genet. 2015 Oct;60(10):589-96. doi: 10.1038/jhg.2015.71. Epub 2015 Jul 2.