About half of the familial breast cancer cases are found to bear mutations in the breast cancer susceptibility gene 1 (BRCA1). The majority of BRCA1 mutations produce a truncated protein and BRCA1-associated breast tumors exhibit a number of defined tumor phenotypes. The function of BRCA1 has been examined in gene knockout mice in which the nullizygous mice die early in utero, but this lethality can be partially rescued by a nullizygous p53 mutation. Wild-type BRCA1 protein binds to a number of cellular proteins, including DNA repair protein Rad51, tumor suppressor p53, RNA polymerase II holoenzyme, RNA helicase A, CtBP-interacting protein, c-myc, BRCA1-associated RING domain protein (BARD1), BRCA2 protein, etc. These proteins likely mediate the involvement of BRCA1 in DNA repair, transcriptional transactivation, and cell cycle control. Overall, BRCA1 protein may act as a converging vehicle for cell regulatory proteins to associate with. Therefore, mutations in BRCA1 may affect the composition of these complexes on which dysregulation of cellular functions with eventual development of malignancy is expected.
To compare the abilities of the nucleic acid dot hybridization assay and the cord blood lymphocyte transformation assay to detect Epstein-Barr virus (EBV), we examined throat washings from healthy control subjects (nine EBV-seronegative and 51 EBV-seropositive), patients with acute infectious mononucleosis, and renal transplant recipients. The dot hybridization assay detected EBV excretion in four (8%) of the EBV-seropositive controls; three of these four were also positive by the lymphocyte transformation assay. Throat washings from seven (87.5%) of eight patients with acute infectious mononucleosis were positive by both assays. EBV was present in throat washings from 13 (50%) of 26 renal transplant recipients. For specimens stored at -70 C for less than four months, the dot hybridization assay had a sensitivity of 90% and a specificity of 98% when compared with the lymphocyte transformation assay. The dot hybridization assay is a rapid, sensitive, and specific test that can be performed on readily available clinical specimens.
Training in molecular pathology in the United States is undergoing development toward a more structured format involving accreditation of training programs and the availability of recognized professional credentials. The traditional apprenticeship for molecular pathology, composed of experience in a molecular biology laboratory with a strong research focus is being replaced by formal training in residency, fellowship, and other postdoctoral training programs that have a clinical focus. This is a reflection of increasing importance of this field to clinical practice, and to a growing desire of persons interested in molecular pathology to undertake formal training programs. These developments are bringing molecular pathology in line with other clinical laboratory specialties for which structured training and certification have long been the norm.An important measure of educational achievement is success in professional examinations leading to recognized credentials. These credentials should attest to the holder's professional competence as a practitioner in the field and are frequently used for this purpose by licensing and other regulatory agencies. In the past decade, and especially in the last 5 years, a number of routes for certification in molecular pathology by examination have been offered by nationally recognized credentialing agencies. This paper provides an update on these certification routes reflective of the growing interest in molecular pathology education.
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