Iulian Gabriel Goidescu, Gabriela Caracostea, Dan Tudor Eniu, Florin Vasile Stamatian
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引用次数: 16
Abstract
Aim: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing is becoming more common in medical care.We report our experience regarding deleterious mutations of high and moderate-risk breast cancer genes (BRCA1/2, TP53, STK11, CDH1, PTEN, PALB2, CHEK2, ATM), as well as more recently identified cancer genes, many of which have increased risk but less well-defined penetrance.
Methods: Genetic testing was performed in 130 consecutive cases with breast cancer referred to our clinic for surgical evaluation and who met the 2016 National Comprehensive Cancer Network (NCCN) criteria for genetic testing.
Results: 82 patients had pathogenic/likely pathogenic mutations and VUS mutations, and 48 were negative; 36 of the pathogenic mutations were in the high-risk genes and 16 were in the moderate risk genes and only 5 cases in the intermediary risk group.From the VUS mutation group 21 cases were in the intermediary risk group, 9 cases were in the moderate risk group and only 7 cases in high risk group.The most frequent BRCA1 variant was c.3607C>T (7 cases) followed by c.5266dupC and c.4035delA (each in 4 cases). Regarding BRCA-2 mutations we identified c.9371A>T and c.8755-1G>A in 6 cases and we diagnosed VUS mutations in 3 cases.
Conclusion: Our study identified 2 mutations in the BRCA1 gene that are less common in the Romanian population, c.3607C>T and c.4035delA. Both variants had particular molecular phenotypes, c.3607C>T variant respecting the triple negative pattern of BRCA1 breast cancer while c.4035delA were Luminal B HER positive.
目的:使用下一代测序技术对遗传性乳腺癌和卵巢癌(HBOC)进行多基因面板检测在医疗保健中越来越普遍。我们报告了我们关于高危和中危乳腺癌基因(BRCA1/2、TP53、STK11、CDH1、PTEN、PALB2、CHEK2、ATM)有害突变的经验,以及最近发现的癌症基因,其中许多风险增加,但外显率不明确。方法:对连续130例符合2016年国家癌症综合网络(NCCN)基因检测标准的乳腺癌患者进行基因检测。结果:致病性/可能致病性突变和VUS突变82例,阴性48例;高危基因36例,中危基因16例,中危组仅有5例。VUS突变组中,中度危险组21例,中度危险组9例,高危组仅有7例。最常见的BRCA1变异是c.3607C>T(7例),其次是c.5266dupC和c.4035delA(各4例)。关于BRCA-2突变,我们鉴定出6例c.9371A>T和c.8755-1G>A,我们诊断出3例VUS突变。结论:我们的研究确定了2种BRCA1基因突变,c.3607C>T和c.4035delA在罗马尼亚人群中不太常见。两种变异体均具有特定的分子表型,c.3607C>T变异体体现BRCA1乳腺癌的三阴性模式,而c.4035delA为Luminal B HER阳性。