Courses >> Conj 539

Conj 539: Biological Basis of Neoplasia

1.  Summary:

This course allows students to gain experience in applying the several disciplines which comprise cellular and molecular biology toward a deeper understanding  of a complex biological problem: neoplastic change.  The course consists of a series of lectures to introduce students to the major themes in research in the cellular and molecular biology of neoplastic change. These are supplemented by in-class student discussions of focus topics lead by a scientist working on the selected problem. Finally students are given take home problem sets which are used for course credit and grading.

The lectures cover principal cancer phenotypes, oncogenes, tumor suppressor genes, genetic instability and mutator phenotypes, loss of tissue homeostasis and senescence and chemical carcinogenesis.  Discussion topics are selected each year.  In past two years they have included: Molecular epidemiology  of breast cancer, genetic mapping of cancer susceptibility genes, molecular probing for clinically undetectable neoplastic cells, discovery of new anti-neoplastic drugs, tumor angiogenesis, apoptosis and cancer, functional genomic analysis of prostate cancer, Epstein-Barr virus and human neoplasia.

2.  Sample selected readings:

Past readings have focussed both on lecture material and on literature specific to the problem sets (which change every year). The instructors pass out a syllabus with a reference list of review articles and syntheses, book chapters and primary papers.  A representive paper would be: Hallmarks of Cancer. Hanahan, D and Weinberg, R.A. Cell. 100(1):57-70, 2000 Jan 7.

3.  List of prerequisite basic principles and concepts:

In terms of preparation a basic understanding of molecular biology ( e.g. essential elements of signal transduction, transcription, translation and the cell division cycle )and genetics from undergraduate and  preceding graduate courses would be desirable.

4. Sample graded questions or assignments from previous year(s):

Take home problem sets involve class-derived information supplemented by student review of literature. Examples of problems:

1. Induction of telomerase activity is associated with a large fraction of human tumors. While investigating a newly classified tumor subtype you find that know of these tumors have activated telomerase. Provide a possible explanation and outline an experiment to test your hypothesis.
2. The P16 tumor suppressor gene is mutated in many human tumor types. Small cell lung cancer is a notable exception where p16 mutations are rarely observed. Suggest three explanations and outline experimental approaches to address them.
3.  Chronic Myelogenous Leukemia (CML) demonstrates a diagnostic 9:22 chromosomal translocation called the Philadelphia (Ph1) chromosome.  This rearrangement fuses the bcr gene on chromosome 22 to the c-abl protooncogene on chromosome 22 resulting in the expression of a tumor-specific fusion protein Bcr/Abl. In most CML patients the clinically detectable leukemic cell population is completely ablated by drug and radiation treatment and marrow transplantation.
   1. Design a sensitive test to detect residual leukemic cells in treated patients present below the level of detection by microscopic examination of blood and marrow samples.
       Using your approach you identify apparently successfully treated patients who have no detectable residual tumor cells, but you also find some who are positive by your test. In long term follow-up studies the test negative patients remain free of disease . Among the patients who tested positive, some relapse but some remain disease free for five or more years.
   2. Assuming that false positive results can be eliminated, explain the test results vs.  clinical outcome for the three groups of patients.  

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