Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Department of Biochemistry, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt.
Clin Exp Med. 2023 Dec;23(8):5063-5088. doi: 10.1007/s10238-023-01207-w. Epub 2023 Oct 7.
This study aimed to identify BRCA1/2 mutational patterns in the tissue and blood of Egyptian colorectal cancer (CRC) patients and to study the possible correlation of this mutational pattern with Human papillomavirus (HPV) infection. Eighty-two colonoscopic biopsies and forty-six blood samples were collected from Egyptian CRC patients, as well as blood samples of age and sex-matched healthy controls (n = 43) were enrolled. The libraries were performed using Qiaseq Human BRCA1 and BRCA2 targeted DNA panel and sequenced via Ion proton sequencer. Also, the CRC tissues were subjected to conventional PCR targeting the HPV Late 1 (L1) region. Our analysis revealed that the BRCA-DNA damage pathway had been altered in more than 65% of the CRC patients. Comparing tissue and blood samples from CRC patients, 25 somatic mutations were found exclusively in tissue, while 41 germline mutations were found exclusively in blood. Additionally, we identified 23 shared BRCA1/2 pathogenic (PVs) mutations in both blood and tissue samples, with a significantly higher frequency in blood samples compared to tissue samples. The most affected exon in BRCA1 was exon 10, while the most affected exons in BRCA2 were 11, 14, 18, 24, and 27 exons. Notably, we revealed an ethnic-related cluster of polymorphism variants in our population closely related to South Asian and African ethnicities. Novel PVs were identified and submitted to the ClinVar database. HPV was found in 23.8% of the CRC tissues, and 54% of HPV-positive cases had somatic BRCA1/2 PVs. The results of this research point to a possible connection between infection with HPV and BRCA1/2 mutations in the occurrence of colorectal cancer in the Egyptian population, which has a mixed ethnic background. Our data also indicate that liquid biopsy (blood samples) may be more representative than tissue samples for detecting BRCA1/2 mutations. These findings may have implications for cancer screening and the development of personalized, targeted therapies, such as PARP inhibitors, which can effectively target BRCA1/2 mutations.
本研究旨在鉴定埃及结直肠癌（CRC）患者组织和血液中的 BRCA1/2 突变模式，并研究这种突变模式与人类乳头瘤病毒（HPV）感染的可能相关性。从埃及 CRC 患者中采集了 82 个结肠镜活检组织和 46 个血液样本，以及年龄和性别匹配的健康对照者（n=43）的血液样本。使用 Qiaseq Human BRCA1 和 BRCA2 靶向 DNA 面板进行文库构建，并通过 Ion proton 测序仪进行测序。此外，对 CRC 组织进行针对 HPV 晚期 1（L1）区域的常规 PCR。我们的分析表明，超过 65%的 CRC 患者的 BRCA-DNA 损伤途径发生了改变。比较 CRC 患者的组织和血液样本，发现 25 个种系突变仅存在于组织中，而 41 个种系突变仅存在于血液中。此外，我们在血液和组织样本中鉴定出 23 个共同的 BRCA1/2 致病性（PV）突变，与组织样本相比，血液样本的频率明显更高。BRCA1 中受影响最严重的外显子是第 10 外显子，而 BRCA2 中受影响最严重的外显子是第 11、14、18、24 和 27 外显子。值得注意的是，我们在本研究人群中发现了与南亚和非洲种族密切相关的种系相关的多态性变异簇。鉴定出了新的 PV 并提交给 ClinVar 数据库。在 23.8%的 CRC 组织中发现了 HPV，54%的 HPV 阳性病例存在种系 BRCA1/2 PV。这项研究的结果表明，HPV 感染与埃及人群结直肠癌中 BRCA1/2 突变之间可能存在联系，而埃及人群具有混合的种族背景。我们的数据还表明，液体活检（血液样本）可能比组织样本更能代表 BRCA1/2 突变的检测。这些发现可能对癌症筛查和开发 PARP 抑制剂等针对 BRCA1/2 突变的个性化靶向治疗具有重要意义。
