title: Utilizing fluorescent life time imaging microscopy technology for identify carriers of BRCA2 mutation.
abstract: 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.
authors.affiliation: Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Zahavi
authors.affiliation: Faculty of Engineering and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Gilad
authors.initials: G
authors.lastname: Yahav
authors.affiliation: Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Shimshon
authors.affiliation: Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel.
authors.forename: Sivan
authors.initials: S
authors.lastname: Gershanov
authors.affiliation: Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Luna
authors.initials: L
authors.lastname: Kaduri
authors.affiliation: Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Sonnenblick
authors.affiliation: Faculty of Engineering and Institute of Nanotechnology and Advanced Materials, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Fixler
authors.affiliation: Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Asher Y
authors.initials: AY
authors.lastname: Salmon
authors.affiliation: Genomic Bioinformatics Laboratory, Department of Molecular Biology, Ariel University, Ariel, Israel. Electronic address: malisa@ariel.ac.il.
authors.forename: Mali
authors.initials: M
authors.lastname: Salmon-Divon
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008856:Microscopy, Fluorescence / Q000379:methods*; D009154:Mutation
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1; BRCA2; FLIM; Irradiation