Molecular Pathology
Duration: One month
Rotation Director(s): Keith Stringer, MD
Faculty/Instructor(s):
David Witte, MD
Kathryn Wikenheiser-Brokamp, MD, PhD
Description of Rotation
The molecular pathology rotation introduces the resident to the analysis of nucleic acid in diagnostic methodologies, including those concerning detection of chromosomal translocation in soft tissue tumors, microbial diagnosis, viral burden, hereditary genetic disorders and oncogene amplification. The resident will be introduced to a variety of technologies, including DNA sequence analysis, Northern, Southern and Western blot analysis, polymerase chain reaction (PCR), reverse transcription PCR, quantitative real-time PCR, fluorescence melting curve analysis, real-time RT-PCR, gel electrophoresis, restriction enzyme digestion, in situ hybridization and fluorescence in situ hybridization (FISH), transcription mediated amplification and Invader technology.
During the course of the four-year training and month rotation, residents will be exposed to a lecture series and discussions with faculty that describe:
- Basic concepts of molecular biology: genetic encoding, transcription, translation, imprinting and basic features of RNA and DNA.
- Concepts of hybridization such as differences in DNA: DNA, DNA: RNA, and RNA: RNA hybrids, basic principles of gel electrophoresis, stringency and restriction digestion
- Methods utilized in molecular pathology, including polymerase chain reaction, restriction enzyme digestion, DNA fingerprinting, in situ hybridization, fluorescence in situ hybridization (FISH) for gene amplification, transcription mediated amplification, and hybrid capture
- Molecular testing of infectious diseases, inherited diseases, solid tumors and hematological disorders
- Future targets for clinically relevant testing, including genomics, proteomics, "chip" analyses etc.
Rotation Objective
- Understand basic concepts of molecular biology and human genetics.
- Become familiar with the theory, performance and clinical interpretation of molecular assays in all four major areas of molecular pathology: infectious diseases, inherited diseases, solid tumors and hematological disorders.
- Understand specimen requirements for molecular tests.
- Understand clinical applications of molecular testing and its relation to other methodologies.
- Develop familiarity with basic administrative, technical, safety and quality control issues important for the operation of the molecular diagnostic lab.
Overall Responsibilities
- The resident will participate in the interpretation of the molecular tests and in issuing the respective molecular diagnostic reports.
- The resident will participate in presentation and discussion of clinical cases at the molecular pathology conferences at CCHMC.
- The resident will participate in molecular pathology (PCR) laboratory weekly meetings.
- The resident will research journal articles and present the clinical and technical aspects of selected diagnostic molecular tests as they relate to medical practice at the Journal Club, Department of Pathology, CCHMC/UC.
Daily Responsibilities
The resident will be provided with reading assignments on the basic principles of molecular biology and diagnostic molecular pathology. The resident will meet several days a week with the director and faculty of the rotation for discussion and review of the assigned literature, interpretation of molecular tests and relevance of test results to clinical practice. The resident will rotate through the different molecular labs where he or she will be able to observe molecular assays in four major areas of molecular pathology.
- Molecular diagnostics of infectious diseases will be observed in the Molecular Pathology Laboratory, Department of Pathology, CCHMC (molecular diagnostics of HSV, EBV, respiratory viruses etc.)
- Molecular diagnostics of solid tumors will be learned in the Molecular Pathology Laboratory, Department of Pathology, CCHMC (real-time RT-PCR for the detection of soft tissue sarcomas).
- Molecular diagnostics of genetic and inherited disorders, including molecular detection of coagulation diseases, will be observed in the Division and Program for Human Genetics at CCHMC (Dr. Kejian Zhang Molecular Genetics Lab).
Evaluation
The resident will be evaluated through daily interaction with the faculty. At the end of rotation, the resident will also be evaluated by a written examination containing multiple choice questions covering major topics of molecular pathology and by the quality of his or her Journal Club presentation.