RNA 测序揭示了先前未解决的林奇综合征家族中具有临床可操作性的种系内含子变异。
RNA sequencing uncovers clinically actionable germline intronic variants in previously unresolved Lynch syndrome families.
机构信息
Ambry Genetics Corp, Aliso Viejo, California, USA
Inova Primary Care, Falls Church, Virginia, USA.
出版信息
BMJ Case Rep. 2022 Apr 29;15(4):e249580. doi: 10.1136/bcr-2022-249580.
Abstract
Despite advances in genetic testing for Lynch syndrome, nearly one quarter of mismatch repair-deficient (MMRd) colorectal and endometrial cancers remain unexplained. When added to germline DNA testing, RNA sequencing can increase diagnostic yield, improve variant classification and reduce variants of uncertain significance. Here, we describe two cases where RNA sequencing uncovered likely pathogenic variants in families with MMRd tumours that were initially unexplained following comprehensive genetic testing for Lynch syndrome.
摘要
尽管在林奇综合征的基因检测方面取得了进展，但近四分之一的错配修复缺陷（MMRd）结直肠癌和子宫内膜癌仍然无法解释。当与种系 DNA 检测联合使用时，RNA 测序可以提高诊断产量，改善变异分类，并减少意义不明的变异。在这里，我们描述了两个案例，在对林奇综合征进行全面基因检测后最初无法解释的 MMRd 肿瘤家族中，RNA 测序发现了可能的致病性变异。
相似文献
1
RNA sequencing uncovers clinically actionable germline intronic variants in previously unresolved Lynch syndrome families.RNA 测序揭示了先前未解决的林奇综合征家族中具有临床可操作性的种系内含子变异。
BMJ Case Rep. 2022 Apr 29;15(4):e249580. doi: 10.1136/bcr-2022-249580.
2
Germline variants screening of MLH1, MSH2, MSH6 and PMS2 genes in 64 Algerian Lynch syndrome families: The first nationwide study.对 64 个阿尔及利亚林奇综合征家族的 MLH1、MSH2、MSH6 和 PMS2 基因进行种系变异筛查：首次全国性研究。
Ann Hum Genet. 2022 Nov;86(6):328-352. doi: 10.1111/ahg.12482. Epub 2022 Sep 8.
3
Advances in genetic technologies result in improved diagnosis of mismatch repair deficiency in colorectal and endometrial cancers.遗传技术的进步导致结直肠癌和子宫内膜癌中错配修复缺陷的诊断得到改善。
J Med Genet. 2022 Apr;59(4):328-334. doi: 10.1136/jmedgenet-2020-107542. Epub 2021 Jan 15.
4
[Genetic analysis of 45 patients with suspected Lynch syndrome using next-generation sequencing].[利用二代测序技术对45例疑似林奇综合征患者进行基因分析]
Zhonghua Zhong Liu Za Zhi. 2021 Aug 23;43(8):843-849. doi: 10.3760/cma.j.cn112152-20190717-00441.
5
Germline MLH1, MSH2 and MSH6 variants in Brazilian patients with colorectal cancer and clinical features suggestive of Lynch Syndrome.巴西结直肠癌患者中与林奇综合征临床特征相关的种系 MLH1、MSH2 和 MSH6 变异。
Cancer Med. 2018 May;7(5):2078-2088. doi: 10.1002/cam4.1316. Epub 2018 Mar 25.
6
Elucidating the molecular basis of MSH2-deficient tumors by combined germline and somatic analysis.通过胚系和体细胞联合分析阐明 MSH2 缺陷型肿瘤的分子基础。
Int J Cancer. 2017 Oct 1;141(7):1365-1380. doi: 10.1002/ijc.30820. Epub 2017 Jul 3.
7
Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report.罕见的种系突变和 MSH2-MSH6 表达在结直肠癌和子宫内膜癌的双原发癌中：一例报告。
Diagn Pathol. 2024 Jan 31;19(1):25. doi: 10.1186/s13000-024-01447-8.
8
Targeted Next-Generation Sequencing of , and Genes in Patients with Endometrial Carcinoma under 50 Years of Age.50 岁以下子宫内膜癌患者中 、 基因的靶向下一代测序。
Balkan Med J. 2019 Jan 1;36(1):37-42. doi: 10.4274/balkanmedj.2018.0922. Epub 2018 Sep 21.
9
Screening for germline mutations of MLH1, MSH2, MSH6 and PMS2 genes in Slovenian colorectal cancer patients: implications for a population specific detection strategy of Lynch syndrome.斯洛文尼亚结直肠癌患者种系 MLH1、MSH2、MSH6 和 PMS2 基因突变的筛查：对林奇综合征人群特异性检测策略的影响。
Fam Cancer. 2009;8(4):421-9. doi: 10.1007/s10689-009-9258-4. Epub 2009 Jun 13.
10
Germline MLH1 and MSH2 mutations in Italian pancreatic cancer patients with suspected Lynch syndrome.意大利疑似林奇综合征的胰腺癌患者中胚系 MLH1 和 MSH2 突变。
Fam Cancer. 2009;8(4):547-53. doi: 10.1007/s10689-009-9285-1.
引用本文的文献
1
Novel MSH6 exon 5-6 skipping variant in a Taiwanese family with Lynch syndrome: implications for genetic testing and cancer management.台湾林奇综合征家族中新型MSH6外显子5-6跳跃变异：对基因检测和癌症管理的意义
Mol Cytogenet. 2025 Mar 11;18(1):5. doi: 10.1186/s13039-025-00708-5.
本文引用的文献
1
Double somatic mismatch repair gene pathogenic variants as common as Lynch syndrome among endometrial cancer patients.子宫内膜癌患者中双体种系错配修复基因突变与林奇综合征一样常见。
Gynecol Oncol. 2021 Jan;160(1):161-168. doi: 10.1016/j.ygyno.2020.10.012. Epub 2020 Oct 21.
2
The Clinical Application of RNA Sequencing in Genetic Diagnosis of Mendelian Disorders.RNA测序在孟德尔疾病基因诊断中的临床应用
Clin Lab Med. 2020 Jun;40(2):121-133. doi: 10.1016/j.cll.2020.02.004.
3
Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes.通过捕获RNA测序得到的剪接图谱可识别肿瘤抑制基因中的致病性种系变异。
NPJ Precis Oncol. 2020 Feb 24;4:4. doi: 10.1038/s41698-020-0109-y. eCollection 2020.
4
Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer.遗传性癌症 RNA 基因检测的诊断结果评估。
JAMA Netw Open. 2019 Oct 2;2(10):e1913900. doi: 10.1001/jamanetworkopen.2019.13900.
5
Clinical characteristics of patients with colorectal cancer with double somatic mismatch repair mutations compared with Lynch syndrome.与林奇综合征相比，具有双重体细胞错配修复突变的结直肠癌患者的临床特征。
J Med Genet. 2019 Jul;56(7):462-470. doi: 10.1136/jmedgenet-2018-105698. Epub 2019 Mar 15.
6
RNA Analysis Identifies Pathogenic Duplications in MSH2 in Patients With Lynch Syndrome.RNA分析鉴定林奇综合征患者MSH2基因的致病性重复。
Gastroenterology. 2019 May;156(6):1924-1925.e4. doi: 10.1053/j.gastro.2019.01.248. Epub 2019 Jan 30.
7
Comprehensive Paired Tumor/Germline Testing for Lynch Syndrome: Bringing Resolution to the Diagnostic Process.全面的肿瘤/胚系配对检测用于林奇综合征：解决诊断过程中的问题。
J Clin Oncol. 2019 Mar 10;37(8):647-657. doi: 10.1200/JCO.18.00696. Epub 2019 Jan 31.
8
Quantitative Analysis of and Germline Splicing Variants Using a Novel RNA-Massively Parallel Sequencing Assay.使用新型RNA大规模平行测序分析对生殖系剪接变体进行定量分析。
Front Oncol. 2018 Jul 27;8:286. doi: 10.3389/fonc.2018.00286. eCollection 2018.
9
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.序列变异解读的标准与指南：美国医学遗传学与基因组学学会和分子病理学协会的联合共识推荐
Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.
10
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.ACG 临床指南：遗传性胃肠道癌综合征的基因检测与管理。
Am J Gastroenterol. 2015 Feb;110(2):223-62; quiz 263. doi: 10.1038/ajg.2014.435. Epub 2015 Feb 3.
Zotero 插件