Resident Manual

Rotation in Molecular Pathology/Cytogenetics

This is a one month rotation for residents to obtain a practical understanding of the molecular and cytogenetic methods likely to see wide use in clinical laboratories over the next few years.  This document covers the Molecular Pathology portion of this rotation.

Molecular Pathology

Introduction

The general goal of the Molecular Pathology rotation is to develop an understanding of when and why to order molecular tests, appreciate some of the technical and financial considerations, understand advantages and disadvantages of each of the clinically relevant technologies, and be semi-skilled in the performance and interpretation of several important nucleic acid-based assays.

The objectives of the rotation are encompassed by the six core competencies as defined by the ACGME and residents will be evaluated during their training in each of these areas.  The above goals will be met through attainment of these six core competencies:

Patient Care that is compassionate, appropriate, and effective for the treatment of health through the following:

• Gather essential and accurate information about patients using all relevant available modalities and incorporate into pathologic interpretations.

• Effectively interpret molecular pathology test results.

• Effectively consult to other clinicians in developing a diagnostic plan, when appropriate, based on specific clinical questions and relevant clinical and pathological information.

• Effectively consult on interpretation or follow-up of unusual or unexpected molecular test results.

Medical Knowledge

• Use all relevant information resources to acquire and evaluate evidence-based information.

• Develop and maintain a knowledge base in the basic and clinical sciences necessary for effective consultation in Molecular Pathology that includes testing for genetic and malignant conditions by PCR, RT-PCR, quantitative real-time PCR, FISH, Invader, Southern blot, sequencing, capillary electrophoresis, and gene arrays.

• Understand the various levels of evidence in medicine and their translation into evidence-based practice.

Practice-based learning and improvement

• Demonstrate the ability to critically assess the scientific literature.

• Demonstrate knowledge of evidence-based medicine and apply its principles in assay development and validation.

• Use multiple sources, including information technology, to optimize life-long learning and support patient care decisions.  

• Develop personally effective strategies for the identification and remediation of gaps in medical knowledge needed for effective practice.

Interpersonal and communication skills

• Demonstrate the ability to write an articulate, legible, and comprehensive yet concise consultation note; provide a clear and informative report, including when appropriate a precise diagnosis, a differential diagnosis, and recommended follow-up or additional studies.

• Demonstrate the ability to provide direct communication to the referring physician or appropriate clinical personnel when interpretation of a laboratory assay reveals an urgent, critical, or unexpected finding and document this communication in an appropriate fashion.

• Demonstrate the ability to work with other clinicians and other health care personnel and administrators to develop clinically advantageous and cost-effective care-delivery strategies.

• Use effective modes and mechanisms of communication.

Professionalism

• Interact with others without discriminating based on religious, ethnic, sexual, or educational differences.

• Demonstrate positive work habits, including punctuality, dependability, and professional appearance.

• Demonstrate principles of confidentiality with all information transmitted both during and outside a patient encounter.

• Demonstrate a commitment to excellence and ongoing professional development.

• Demonstrate interpersonal skills in functioning as a member of a multidisciplinary health care team.

Systems-based practice

• Demonstrate understanding of the role of the clinical laboratory in the health care system.

• Demonstrate the ability to design resource-effective diagnostic plans based on knowledge of best practices in collaboration with other clinicians.

• Demonstrate knowledge of basic health care reimbursement methods.

• Demonstrate knowledge of the laboratory regulatory environment including issues related to home-brew assay development and validation.

Service Responsibilities

There are no direct service responsibilities during this rotation.  However, molecular results on patients will be reviewed with the medical director.  The resident on the Molecular Pathology rotation may take Clinical Pathology or Anatomic Pathology call.

Specific Topic and Reading Assignments

Molecular Biology

Computer-based Molecular Biology Primer:

Nucleic acid structure and properties

Cell cycle

DNA replication and key enzymes

Gene structure and organization

Transcription and translation

Gene regulation

Reverse transcription

Endo- and exonucleases

Reading:  Coleman and Tsongalis. Molecular Diagnostics for the Clinical Laboratorian (2^nd Ed.). Totowa, NJ: Humana Press, 2006, Chapter 2.

DNA/RNA Extraction

Computer-based Tutorial:

Organic extraction virtual lab

Purity

Stability and storage

Laboratory I:

DNA extraction from whole blood

Pico Green to measure quantity

Store for future PCR lab

Molecular Techniques Overview

Computer-based Tutorial:

History

Restriction enzymes

Southern blotting

Northern and western blotting

DNA sequencing

PCR

FISH

Invader

PCR/RT-PCR

Computer-based Tutorial:

Reaction conditions

Primer design

Contamination issues

Amplicon detection methods

Amplicon confirmation:

     probes, nesting, RFLP, SSCP, sequencing

Reading: Coleman and Tsongalis. Molecular Diagnostics for the Clinical Laboratorian (2^nd Ed.). Totowa, NJ: Humana Press, 2006, Chapters 5, 7, and 9 pages 85-92.

Assay development and validation

Computer-based “Home brew” exercise (FLT3):

Literature review

Primer and reaction condition selection

Validation of procedure

Laboratory II     

Amplify FLT3 (PCR)

Laboratory III    

Digest, separate, identify amplicon

Overview of genetic testing

Computer-based tutorial:

HIPPA

Applications

Risk calculations

Screening programs versus diagnostic w/u

Inheritance patterns

Ethics and genetic counseling

Common Genetic Disorders

Computer-based tutorial:

CF, FV Leiden, Prothrombin G20210A,

Hemoglobinopathies, Hemachromatosis,

Prader Willi, etc.

Methods of detection

Intellectual property issues

Counseling and reporting issues

Case studies

Laboratory IV

Set-up Invader assay for Factor V Leiden

Laboratory V    

Read and interpret Invader results

Reading: Coleman and Tsongalis. Molecular Diagnostics for the Clinical Laboratorian (2^nd Ed.). Totowa, NJ: Humana Press, 2006, Chapters 22 and 28

Hematology/Oncology Overview

Computer-based tutorial:

History

Applications

Clonality versus aberrant genes

Gene rearrangements

Computer-based tutorial:

Immunologic gene rearrangement

Detecting gene rearrangements

Detection by Southern blot technique

Detection by PCR (gel versus capillary)

Case studies

Translocations and oncogenes

Computer-based tutorial:

Leukemias

Lymphomas

Sarcomas

Breast cancer

PCR/RT-PCR versus FISH

MRD detection

Reading: Coleman and Tsongalis. Molecular Diagnostics for the Clinical Laboratorian (2^nd Ed.). Totowa, NJ: Humana Press, 2006, Chapters 32 and 33

FISH testing

Computer-based tutorial:

Technical overview

Laboratory VI:

Set-up FISH assay

Laboratory VII  

Wash and counter stain

Read slides and interpret results with Medical Director

Reading: Coleman and Tsongalis. Molecular Diagnostics for the Clinical Laboratorian (2^nd Ed.). Totowa, NJ: Humana Press, 2006, Chapter 15

Quality Assurance

Reading: Coleman and Tsongalis. Molecular Diagnostics for the Clinical Laboratorian (2^nd Ed.). Totowa, NJ: Humana Press, 2006, Chapters 18-21

Residents at all levels will pursue a similar course of instruction.  Although it is not a goal of the rotation that the resident becomes technically expert in laboratory procedures, the resident must gain an understanding of the technical aspects of each procedure.  Adjustment may be made for those with prior molecular biology experience. 

While research projects are welcome at any time, this rotation is explicitly not aimed at producing lab results, but rather at understanding what molecular pathology is and is likely to become.

Evaluation

Evaluation will be performed by the Molecular Diagnostics Medical Director.  Criteria used will include attendance, effort in performing bench work, and an informal assessment of knowledge gained from reading and didactic sessions with attention to integration of the knowledge with experience at the lab bench.

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