巴基斯坦一个未选择的胰腺癌患者队列中BRCA1和BRCA2种系变异的患病率

IF 2 4区医学 Q3 ONCOLOGY

Hereditary Cancer in Clinical Practice Pub Date : 2023-11-11 DOI:10.1186/s13053-023-00269-x

Noor Muhammad, Ayesha Azeem, Shumaila Arif, Humaira Naeemi, Iqra Masood, Usman Hassan, Bushra Ijaz, Faisal Hanif, Aamir Ali Syed, Muhammed Aasim Yusuf, Muhammad Usman Rashid

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引用次数: 0

摘要

背景:BRCA1和BRCA2 (BRCA1/2)是白种人胰腺癌患者中最常研究的基因，而亚洲人的报道有限。我们的目的是调查BRCA1/2种系变异在巴基斯坦胰腺癌患者中的患病率。方法:采用变性高效液相色谱和高分辨率熔解分析对150例未入选和前瞻性入选的胰腺癌患者进行BRCA1/2种系变异的全面筛选，然后对变异片段进行DNA测序。利用计算机工具分析了这些新变异的致病作用。在200名无癌对照中进一步筛选了潜在的功能性变异。结果:仅在BRCA2中检测到蛋白截断变异，患病率为0.7%(1/150)。在一名有腹部癌症家族史的71岁帕坦族男性患者中发现移码BRCA2变异(p.Asp946Ilefs*14)。此外，我们在BRCA2中发现了一个新的变异(p.Glu2650Gln)，在BRCA1中发现了两个先前报道的变异(p.g thr293ser)和BRCA2中发现了两个变异(p.g ile2296leu)，在BRCA2中发现了一个复发的无义变异(p.g lys3326ter)。这些变异被归类为不确定意义变异(VUS)。值得注意的是，这些VUS携带者都没有胰腺癌或其他癌症的家族史。结论:在第一项研究中，BRCA1/2致病性变异在巴基斯坦胰腺癌患者中发现频率较低。建议在巴基斯坦胰腺癌患者中进行全面的多基因面板检测，以加强对该人群的遗传理解。

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Prevalence of BRCA1 and BRCA2 germline variants in an unselected pancreatic cancer patient cohort in Pakistan.

Background: BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients.

Methods: One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls.

Results: Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers.

Conclusions: In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.

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来源期刊

Hereditary Cancer in Clinical Practice 医学-肿瘤学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.