[1]马占忠,许红雁,胡红波,等.靶向高通量测序检测卵巢癌患者易感基因突变与临床特征的相关性研究[J].现代检验医学杂志,2021,36(06):111-115.[doi:10.3969/j.issn.1671-7414.2021.06.023]
　MA Zhan-zhong,XU Hong-yan,HU Hong-bo,et al.Targeted High-Throughput Sequencing to Detect the Correlation between Susceptible Gene Mutations and Clinical Features in Patients with Ovarian Cancer[J].Journal of Modern Laboratory Medicine,2021,36(06):111-115.[doi:10.3969/j.issn.1671-7414.2021.06.023]
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靶向高通量测序检测卵巢癌患者易感基因突变与临床特征的相关性研究()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第36卷
期数:
2021年06期
页码:
111-115
栏目:
论　著
出版日期:
2021-12-15

文章信息/Info

Title:
Targeted High-Throughput Sequencing to Detect the Correlation between Susceptible Gene Mutations and Clinical Features in Patients with Ovarian Cancer
文章编号:
1671-7414（2021）06-111-05
作者:
马占忠; 许红雁; 胡红波; 等
（汕头大学医学院附属粤北人民医院 a. 检验科；b. 妇科；c. 生物样本库，广东韶关 512026）
Author(s):
MA Zhan-zhong;  XU Hong-yan;  HU Hong-bo;  et al
（a. Department of Clinical Laboratory; b. Department of Gynecology; c. Biobank , Yuebei People’s Hospital Affiliated to Shantou University Medical College, Guangdong Shaoguan 512026, China）
关键词:
高通量测序; 卵巢癌; 基因突变; BRCA1/2
分类号:
R737.31；R730.43
DOI:
10.3969/j.issn.1671-7414.2021.06.023
文献标志码:
A
摘要:
目的　探讨卵巢癌易感基因突变与临床特征的关系。方法　采用靶向高通量测序技术对35例卵巢癌患者的外周血进行BRCA1，BRCA2，CHEK2，PALB2，BRIP1，TP53，PTEN，STK11，CDH1，ATM，BARD1，MLH1，MRE11A，MSH2，MSH6，MUTYH，NBN，PMS1，PMS2，RAD50和RAD51C共21种易感基因进行测序，结合临床资料分析基因突变与卵巢癌的相关性。结果　卵巢癌患者多以高级别浆液性卵巢癌晚期为主。35例卵巢癌患者中共检出已知致病突变19例，突变率54.3%，其中BRCA1基因突变7例（20.0%），BRCA2基因突变4例（11.4%），RAD51C基因突变2例（5.7%），CHEK2，ATM，RAD50，MSH2，MRE11A和TP53基因突变各1例。BRCA1/2基因突变和高级别浆液性卵巢癌相关（P=0.034），和家族史显著相关（P=0.003），与年龄、FIGO分期无显著相关性（P>0.05）。另外，发现两种新的基因突变，包括BRCA1基因c.438delC和RAD51C基因c.390_391delAA。结论　BRCA1和BRCA2是卵巢癌最主要的胚系突变基因，该基因突变与遗传性卵巢癌显著相关。高通量基因测序技术可有效检测卵巢癌胚系易感基因的突变情况，为卵巢癌的早期诊断和预防提供科学依据。
Abstract:
Objective　To investigate the relationship between ovarian cancer susceptibility gene mutations and clinical features. Methods　Using target high-throughput sequencing technology to perform BRCA1, BRCA2, CHEK2, PALB2, BRIP1, TP53, PTEN, STK11, CDH1, ATM, BARD1, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, RAD50 and RAD51C, a total of 21 susceptible gene were sequenced in 35 patients with ovarian cancer, and the correlation between gene mutations and ovarian cancer was analyzed based on clinical data. Results　The patients with ovarian cancer were mostly high-grade serous ovarian cancer at the advanced stage. A total of 19 cases of known pathogenic mutations were detected in 35 cases of ovarian cancer, with a mutation rate of 54.3%, including 7 cases of BRCA1 gene mutation (20.0%), 4 cases of BRCA2 gene mutation (11.4%), and 2 cases of RAD51C gene mutation (5.7%) , CHEK2, ATM, RAD50, MSH2, MRE11A and TP53 gene mutations in 1 case each. BRCA1/2 gene mutation was correlated with high-grade serous ovarian cancer (P=0.034), and significantly correlated with family history (P=0.003), but not significantly correlated with age and FIGO staging (P>0.05). Furthermore, two new gene mutations have been discovered, including the BRCA1 gene c.438delC and the RAD51C gene c.390_391delAA. Conclusion　BRCA1 and BRCA2 are the most important germline mutant genes in ovarian cancer, and significantly related to hereditary ovarian cancer. High-throughput gene sequencing technology can effectively detect the mutations of ovarian cancer susceptible genes and provide scientific basis for early diagnosis and prevention of ovarian cancer.

参考文献/References:

[1] FERLAY J, COLOMBET M, SOERJOMATARAM I, etal. Estimating the global cancer incidence and mortalityin 2018: GLOBOCAN sources and methods[J].International Journal of Cancer, 2019, 144(8): 1941-1953.
[2] World Health Organization (WHO). WHO methods anddata sources for country-level causes of death 2000-2019[EB/OL]. https://www.who.int/data/global-healthestimates,2020.
[3] 马同敏, 赵志强. 血清CA125,STIP1 和IGF- Ⅰ联合检测对卵巢癌的早期诊断价值研究[J]. 现代检验医学杂志,2018,33(6):50-54, 58.MA Tongmin, ZHAO Zhiqiang. Clinical value ofcombined detection of serum CA125,STIP1 and IGF-Ilevels in early diagnosis of ovarian cancer [J]. Journalof Modern Laboratory Medicine, 2018, 33(6): 50-54,58.
[4] SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics,2018[J]. CA-A Cancer Journal for Clinicians,2018, 68(1): 7-30.
[5] ALLEMANI C, WEIR H K, CARREIRA H, et al.Global surveillance of cancer survival 1995-2009:analysis of individual data for 25 676 887 patientsfrom 279 population-based registries in 67 countries(CONCORD-2)[J]. Lancet, 2015, 385(9972): 977-1010.
[6] MURAKAMI R, MATSUMURA N, MANDAI M,et al. Establishment of a novel histopathologicalclassification of high-grade serous ovarian carcinomacorrelated with prognostically distinct gene expressionsubtypes[J]. The American Journal of Pathology, 2016,186(5): 1103-1113.
[7] BATTISTA M J, COTARELO C, ALMSTEDT K,et al. Validation of a two-tier grading system in anunselected, consecutive cohort of serous ovarian cancerpatients[J]. Archives of Gynecology and Obstetrics,2016, 294(3): 599-606.
[8] LEWIS K E, LU K H, KLIMCZAK A M, et al.Recommendations and choices for BRCA mutationcarriers at risk for ovarian cancer: a complicateddecision[J]. Cancers, 2018, 10(2): 57.
[9] 左珂, 杨文涛. 累及女性生殖系统的遗传性肿瘤综合征概述[J]. 中华病理学杂志, 2017, 46(9):655-658.ZUO Ke, YANG Wentao. Overview of hereditary tumorsyndromes involving the female reproductive system[J]. Chinese Journal of Pathology, 2017, 46(9):655-658.
[10] The AACR Project GENIE Consortium. AACR ProjectGENIE: Powering precision medicine through aninternational consortium[J].Cancer discovery, 2017,7(8) : 818-831.
[11] AMIN N, CHAABOUNI N, GEORGE A. Genetictesting for epithelial ovarian cancer[J]. Best Practice &Research Clinical Obstetrics & Gynaecology, 2020, 65:125-138.
[12] BARNES D R, ROOKUS M A, MCGUFFOG L, etal. Polygenic risk scores and breast and epithelialovarian cancer risks for carriers of BRCA1 and BRCA2pathogenic variants[J]. Genetics in Medicine, 2020,22(10): 1653-1666.
[13] VAROL U, KUCUKZEYBEK Y, ALACACIOGLU A,et al. BRCA genes: BRCA 1 and BRCA 2[J]. Journal ofB.U.ON, 2018, 23(4): 862-866.
[14] 刘畅, 马寅婷, 卓钟灵, 等. 应用二代测序技术检测乳腺癌易感基因BRCA1/2 和TP53 及PTEN 胚系突变[J]. 中华检验医学杂志,2019,42(2):98-103.LIU Chang, MA Yinting, ZHUO Zhongling, et al.Application of next-generation sequencing in detectionof breast cancer susceptibility genes BRCA1/2,TP53and PTEN germline mutation [J]. Chinese Journal ofLaboratory Medicine, 2019, 42(2):98-103.
[15] DALY M B, PAL T, BERRY M P, et al. Genetic/familialHigh-Risk assessment: breast, ovarian, and pancreatic,version 2.2021, NCCN clinical practice guidelines inoncology[J]. Journal of the National ComprehensiveCancer Network, 2021, 19(1): 77-102.
[16] KWONG A, CHEUK I W, SHIN V Y, et al. Somaticmutation profiling in BRCA-negative breast and ovariancancer patients by multigene panel sequencing[J].American Journal of Cancer Research, 2020, 10(9):2919-2932.
[17] GARZIERA M, RONCATO R, MONTICO M, etal. New challenges in tumor mutation heterogeneityin advanced ovarian cancer by a targeted nextgenerationsequencing (NGS) approach[J]. Cells (Basel,Switzerland), 2019, 8(6): 584.
[18] WU Huanwen, XU Binghe, GAO Qinglei,et al.Discrepancies in genetic testing procedures ofBRCA1/2 mutations: a National survey across China[J].Molecular Diagnosis & Therapy, 2020, 24(6): 715-721.
[19] BASU N N, HODSON J, CHATTERJEE S, et al.The Angelina Jolie effect: contralateral risk-reducingmastectomy trends in patients at increased risk of breastcancer[J]. Scientific Reports, 2021, 11(1): 2847.
[20] 黄林. 预防性卵巢切除对预防卵巢癌的价值及可行性[J]. 中国计划生育和妇产科, 2014, 6 (2):6-9.HUANG Lin. The value and feasibility of prophylacticoophorectomy for ovarian carcinoma prevention [J].Chinese Journal of Family Planning & Gynecotokology,2014, 6 (2):6-9.
[21] Breast Cancer Association Consortium, DORLINGL, CARVALHO S, et al. Breast cancer risk genes -association analysis in more than 113 000 women[J].The New England Journal of Medicine, 2021, 384(5):428-439.
[22] 何佳雪, 姜艳芳. 高通量测序技术在临床诊治遗传性肿瘤中的应用与研究进展[J]．中华预防医学杂志，2017, 51(8):772-776.HE Jiaxue, JIANG Yanfang. The progress and prospectof application of genetic testing technology-based genedetection technology in the diagnosis and treatment ofhereditary cancer [J]. Chinese Journal of PreventiveMedicine, 2017, 51(8):772-776.
[23] 中国临床肿瘤学会肿瘤标志物专家委员会, 中国肿瘤驱动基因分析联盟. 二代测序技术在肿瘤精准医学诊断中的应用专家共识[J]. 中华医学杂志, 2018,98(26):2057-2065.Umor Marker Expert Committee of Chinese Societyof Clinical Oncology,China Tumor Driver GeneAnalysis Alliance. Experts in the application of secondgenerationsequencing technology in tumor precisionmedical diagnosis consensus [J]. National MedicalJournal of China, 2018, 98(26):2057-2065.
[24] 程亚楠, 于津浦. 肿瘤大基因包高通量测序在临床中的应用进展[J]. 中国肿瘤临床,2019,46(2):94-98.CHENG Yanan,YU Jingpu. Advances in the clinicalapplications of large panel high-throughput sequencingin tumors [J]. Chinese Journal of Clinical Oncology,2019, 46(2):94-98.
[25] 基于下一代测序技术的BRCA1/2 基因检测指南编写组. 基于下一代测序技术的BRCA1/2 基因检测指南(2019 版)[J]. 中华病理学杂志,2019,48(9):670-677.Working Group of Guideline on Next-generation Sequencing-based BRCA1/2 TESTING (2019). Guidelineon next-generation sequencing-based BRCA1/2 testing(2019)[J]. Chin J Pathol, 2019, 48(9):670-677.
[26] KUROKI L, GUNTUPALLI S R. Treatment ofepithelial ovarian cancer[J]. BMJ (Online), 2020, 371:m3773.

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更新日期/Last Update: 1900-01-01