Loutfy Samah A, Abdallah Zeinab F, Shaalan Mohamed, Moneer Mohamed, Karam Adel, Moneer Manar M, Sayed Ibrahim M, Abd El-Hafeez Amer Ali, Ghosh Pradipta, Zekri Abdel-Rahman N
Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Cancer Manag Res. 2021 Mar 26;13:2835-2848. doi: 10.2147/CMAR.S294584. eCollection 2021.
Mouse mammary tumor virus (MMTV) is thought to have a role in human breast cancer (BC) pathogenesis. BRCA1 and 2 genes mutations are well-established risk factors for BC. The purpose of this study was to evaluate the presence of MMTV in familial and non-familial Egyptian breast cancer patients. We also aimed to establish a correlation between BRCAs genes mutations and MMTV infection in those patients.
The study was included 80 BC patients and 10 healthy women were included as a control group. We used PCR to amplify a 250-bp MMTV-like env sequence. We also used PCR followed by direct sequencing to identify the genetic variation of exons 2, 13, 19 of BRCA1 gene and exon 9 and region f of exon 11 of BRCA2 gene. High resolution melting (HRM) analysis was used to screen the selected exons of BRCA1/2 genes in order to detect different variants.
MMTV DNA-like env sequences were detected in 70%, 76% of familial and non-familial BC patients, respectively, and it was not detected in any of the control subjects. The presence of viral sequences was associated with larger tumor size in the sporadic patients. Seventy BC patients showed variations in BRCA1/2 genes according to HRM analysis and sequencing analysis showed two different sequences of polymorphism among 22 familial and non-familial BC patients.
MMTV DNA was present among BC patients and it was associated with increased tumor growth. This indicates a potential role for MMTV in BC patients with and without deleterious mutation in BRCA1/2 genes.
小鼠乳腺肿瘤病毒(MMTV)被认为在人类乳腺癌(BC)发病机制中起作用。BRCA1和2基因突变是公认的乳腺癌风险因素。本研究的目的是评估埃及家族性和非家族性乳腺癌患者中MMTV的存在情况。我们还旨在确定这些患者中BRCA基因的突变与MMTV感染之间的相关性。
该研究纳入了80例乳腺癌患者,并纳入10名健康女性作为对照组。我们使用聚合酶链反应(PCR)扩增一段250bp的MMTV样env序列。我们还使用PCR随后直接测序来鉴定BRCA1基因外显子2、13、19以及BRCA2基因外显子9和外显子11区域f的基因变异。高分辨率熔解(HRM)分析用于筛选BRCA1/2基因的选定外显子,以检测不同的变异。
分别在70%的家族性和76%的非家族性乳腺癌患者中检测到MMTV DNA样env序列,而在任何对照受试者中均未检测到。在散发性患者中,病毒序列的存在与更大的肿瘤大小相关。根据HRM分析,70例乳腺癌患者显示BRCA1/2基因存在变异,测序分析显示22例家族性和非家族性乳腺癌患者中有两种不同的多态性序列。
MMTV DNA存在于乳腺癌患者中,并且与肿瘤生长增加相关。这表明MMTV在BRCA1/2基因有无有害突变的乳腺癌患者中均具有潜在作用。