目的:下一代测序(NGS)技术在遗传性癌症遗传调查中的应用对于临床监测非常重要,治疗方法,并降低发展新的恶性肿瘤的风险。该研究的目的是探索遗传性癌症患者的遗传易感性。
方法:共有8,261名个体接受多基因基因检测,在2020-2023年期间,在实验室,并使用NGS进行了多基因基因基因检测。在被检查的个人中,56.17%被诊断为乳腺癌,6.77%患有卵巢癌,2.88%患有结直肠癌,1.91%患有前列腺癌,6.43%健康,有明显的癌症家族史,3.06%患有不同类型的癌症,0.21%未提供任何信息。此外,在85例乳腺癌患者中,我们进行了全外显子组测序分析.
结果:20%的受检个体携带致病性变异。具体来说,54.8%的患者在临床显著基因(BRCA1、BRCA2、PALB2、RAD51C、PMS2,CDKN2A,MLH1,MSH2,TP53,MSH6,APC,RAD51D,PTEN,RET,CDH1、MEN1和VHL)。在检测到的不同类型的致病变异中,显著百分比(6.52%)代表拷贝数变异(CNV)。通过WES分析,检测到以下发现:CTC1:c.880C>T,p.(Gln294*);MLH3:c.405del,p.(Asp136Metfs*2),PPM1D:c.1426_1430del,p.(Glu476Leufs*3),SDHB:c.395A>G,p.(His132Arg)。
结论:全面的多基因基因检测对于对致病变异携带者进行适当的临床管理是必要的。此外,所获得的信息对于确定受检个体家庭成员发生恶性肿瘤的风险非常重要.
OBJECTIVE: The application of next-generation sequencing (NGS) technology in the genetic investigation of hereditary cancer is important for clinical surveillance, therapeutic approach, and reducing the risk of developing new malignancies. The aim of the study was to explore genetic predisposition in individuals referred for hereditary cancer.
METHODS: A total of 8,261 individuals were referred for multigene genetic testing, during the period 2020-2023, in the laboratory, and underwent multigene genetic testing using NGS. Among the examined individuals, 56.17% were diagnosed with breast cancer, 6.77% with ovarian cancer, 2.88% with colorectal cancer, 1.91% with prostate cancer, 6.43% were healthy with a significant family history of cancer, while 3.06% had a different type of cancer and 0.21% had not provided any information. Additionally, in 85 women with breast cancer we performed whole exome sequencing analysis.
RESULTS: 20% of the examined individuals carried a pathogenic variant. Specifically, 54.8% of the patients had a pathogenic variant in a clinically significant gene (BRCA1, BRCA2, PALB2, RAD51C, PMS2, CDKN2A, MLH1, MSH2, TP53, MSH6, APC, RAD51D, PTEN, RET, CDH1, MEN1, and VHL). Among the different types of pathogenic variants detected, a significant percentage (6.52%) represented copy number variation (CNV). With WES analysis, the following findings were detected: CTC1: c.880C>T, p.(Gln294*); MLH3: c.405del, p.(Asp136Metfs*2), PPM1D: c.1426_1430del, p.(Glu476Leufs*3), and SDHB: c.395A>G, p.(His132Arg).
CONCLUSIONS: Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants\' carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals.