Zahavi Tamar, Yahav Gilad, Shimshon Yael, Gershanov Sivan, Kaduri Luna, Sonnenblick Amir, Fixler Dror, Salmon Asher Y, Salmon-Divon Mali
Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
Faculty of Engineering and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.
Biochem Biophys Res Commun. 2016 Nov 4;480(1):36-41. doi: 10.1016/j.bbrc.2016.10.013. Epub 2016 Oct 6.
Worldwide, more than one million women are diagnosed with breast cancer every year, making it the most common female malignancy in the developed world. Germline mutations in BRCA1 and BRCA2 genes are estimated to increase the risk for developing breast cancer by up to 87%. From a clinical point of view, identification of BRCA1 and BRCA2 mutation carriers offers an opportunity to early identify or prevent the development of malignancy; therefore the ability to determine which women are more likely to carry BRCA1 or BRCA2 mutations is of great importance. The available diagnostic tests for mutation analysis of BRCA1 and BRCA2 are time- and labor-intensive, expensive, and do not allow the identification of all the functional mutations. We utilized the Fluorescent lifetime (FLT) imaging microscopy method which allows recognizing different cell populations, in order to distinguish between lymphocytes from BRCA1 and BRCA2 mutation carriers and non-carrier women by using easily obtainable lymphocyte cells from peripheral blood. Our results demonstrate that cells originated from BRCA2-mutation carriers have significantly lower FLT values compared with BRCA1 mutation carriers and control cells. This simple, inexpensive and sensitive method may be utilized in the future to detect BRCA2 mutation carriers, particularly those bearing unknown functional mutations.
在全球范围内，每年有超过100万女性被诊断出患有乳腺癌，这使其成为发达国家最常见的女性恶性肿瘤。据估计，BRCA1和BRCA2基因的种系突变会使患乳腺癌的风险增加高达87%。从临床角度来看，识别BRCA1和BRCA2突变携带者为早期识别或预防恶性肿瘤的发展提供了机会；因此，确定哪些女性更有可能携带BRCA1或BRCA2突变的能力至关重要。现有的用于BRCA1和BRCA2突变分析的诊断测试耗时费力、成本高昂，并且无法识别所有功能性突变。我们利用荧光寿命（FLT）成像显微镜方法来识别不同的细胞群体，以便通过使用外周血中易于获取的淋巴细胞来区分BRCA1和BRCA2突变携带者以及非携带者女性的淋巴细胞。我们的结果表明，与BRCA1突变携带者和对照细胞相比，源自BRCA2突变携带者的细胞具有显著更低的FLT值。这种简单、廉价且灵敏的方法未来可能用于检测BRCA2突变携带者，特别是那些携带未知功能性突变的携带者。
