Cancer Genomics (3 credit)
4:30 pm - 7:10 pm (Thursdays)
Prince William: Bull Run Hall 248
Instructor: Dr. Ancha Baranova
Email: abaranov@gmu.edu Phone: 571-334-1145 cell.
Please email or call me if you need my help. I mean it.
Course objectives:
This course in cancer genomics will review the modern concepts in cancer biology. We will discuss
histological and molecular taxonomy of human tumors, and common syndromes associated with increased
probability of tumor development. We will highlight genomic instability as a central player that is important for
cancer initiation, progression and response to chemotherapeutic agents. We will go through both position–dependent
and position-independent strategies allowing one to discover genes involved in human tumor development. We will
also focus on high-throughput methods of cancer research, including various methods of expression profiling. A
systematic review of molecular pathways involved in cancer development will be presented in the course. This will
involve a detailed study of molecular consequences of oncogene activation and tumor suppressor gene inactivation.
We will untangle the molecular network underlying cell death and cell proliferation in cancer, as well as tumor cell
invasion, migration and induction of angiogenesis. Also we will review examples of therapeutic agents that
specifically "target" tumor cells in order to prevent, diagnose, treat, and provide follow-up surveillance of cancer.
Text: The Biology of Cancer by Robert A. Weinberg,
Garland Science, 2006. Kindle edition is available.
WEEK
August
30th
September
6th
September
13th
TOPICs
1. Cancer epidemiology
2. Classification of human tumors
3. Tumor histology – grading and staging
4. Types of available cancer treatments
5. Principles of chemotherapy
6. Types of common chemotherapeutic drugs
7. Drug resistance in cancer
8. Tumor progression and natural course of tumor development
9. Genes are mutated/ deleted/altered in tumors
10. Multistep model of cancer progression
11. Clonal selection in human tumors.
12. Metastasis as a product of cell evolution.
13. Angiogenesis
14. How tumor cells evade immune system
15. Organ specificity of metastasis
16. Types of carcinogenesis
17. Sporadic tumors and Inherited cancer syndromes (augment 9.)
18. Types of genes involved in the tumorigenesis
CHAPTER
2, 16
2, 11, 4, 15,
13, 14
3, 11, 12
19. Tumor suppressor genes and oncogenes.
September
20th
September
27th
October
4th
MID-TERM EXAM I
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
October
11th
October
18th
October
25th
Biomarkers lecture (III-B) stats
Instability of the genome as a fundamental feature of a cancer cell
Types of mutations. MIN, CIN, SIN.
Telomeres, telomerase and cancer
DNA repair. XP as an example
Concept of the checkpiont
AT as an example
PARP
DNA-PKs, NHEJ, SCID
Role of BRCA1 and 2 genes in DNA repair
The story of TP53, mechanisms of action, MDM2-dependent
degradation
Basics of Epigenetics
DNA methylations and demethylation in human tumors
Long non-coding RNAs in tumors, HOTAIR and other examples
Alternative splicing in human tumors. Examples
CpG methylator phenotype
DNA methylation and histone code in ageing; connection to
tumorigenesis
HDAC. HDAC inhibitors as as anticancer drgs
MID-TERM EXAM II
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
Apoptosis and necrosis
Caspases
Bcl-2 and bax
Death receptors
TNF-alpha signaling
Myc-Max network
Leukemic translocation
Blood cell and leukemia differentiation
BCR/ABL, Gleevec
Retinoic acid as differentiator, PML-RAR-alpha and arsenic
Cancer gene cloning strategies, positional cloning
FISH, CGH, LOH
Differential display
Comparative genomics approaches
SAGE, Microarray
Mutational screening
Promoter methylation
Functional assays on tumorigenecity
Biomarkers and phage dispaly
4, 11, 7, 12
11,12
NO
CHAPTER
6, 7
5, 6, 7
May be absorption break with paper–reading
homework (papers will be given).
Dr. Agarwal lecture as a homework
(Inflammation, antioxidant and cancer)
13
MID-TERM EXAM III
5,6
November
1st
57.
58.
59.
60.
TGF-beta pathway/ SMADs
WNT – catenin-β signaling pathway/ APC
Growth factors and their receptors
RAS as a switch / NF1
November
8th
November
15th
November
22nd
November
28th
December
6th
December
13th
61.
62.
63.
64.
65.
18.
19.
20.
PTEN phosphatase
Extracellular matrix signaling in tumors
Cadherins, integrins, Focal adhesion
CD44 protein family
Hypoxia in tumors and VHL suppressor
Cell cycle network
Retinoblastoma RB1 and cyclins
CDK inhibitors, p51, p27, p57
INK4-family of CDK inhibitors and ARF
NO CLASS (Thanksgiving)
5,6,13
9
18.
19.
20.
21.
Cancer-associated polymorphisms
H-RAS, TP53 ARG/ARG
Treatment response
Phase I and Phase I enzymes, GSTP, MTHFR
Antioxidants
Remainders of the material. Overview of the difficult moments
FINAL EXAM
Grading:
Midterm exam I
Midterm exam II
Midterm exam II
Final exam (Specific)
Final Exam (cumulative)
In Class discussions
and teacher points
100pts
100 pts
100 pts
100pts
100 pts
20%
20%
20%
20%
20%
5% (on top of everything)
You may choose to drop ONE of the mid-term exams and substitute it with your grade at CUMULATIVE
part of the Final exam. The decision to drop ONE of the Mid-Term exams shall be told to Dr. Baranova one
week BEFORE Final Exam.
Important: Exams are not repeatable. When you sign up for this class, you are committing
to come to the class for Exams.
All exams will be written form.
Letter grades for the course will be assigned as follows:
Grade
Overall %
A
AB+
B
C
F
>90
85-89.9
80-84.9
70-79.9
60-69.9
<69.9
The final exam will be given according to the university schedule. Curve will be applied if necessary.
IMPORTANT:
IN CASE YOU HAVE NO CLUE
WHAT WE ARE TALKING ABOUT
IN MOLECULAR LECTURES:
DNA replication, mitosis and meiosis, chromatin
http://www.youtube.com/watch?v=teV62zrm2P0&feature=related
http://www.youtube.com/watch?v=4PKjF7OumYo&feature=related
http://www.youtube.com/watch?v=sJCWVTnFf5o&feature=related
http://www.youtube.com/watch?v=lf9rcqifx34&feature=related
http://www.youtube.com/watch?v=bwVjYxcDQ5I
Transcription, processing, splicing, alternative splicing,
transcription factors
http://vcell.ndsu.edu/animations/transcription/movie-flash.htm
http://vcell.ndsu.edu/animations/mrnaprocessing/movie-flash.htm
http://www.youtube.com/watch?v=4X8eK15R8yY&feature=related
http://www.youtube.com/watch?v=Dxyq8GAWbpo&feature=related
Cells signaling and protein modification
http://www.youtube.com/watch?v=U6uHotlXvPo
http://www.youtube.com/watch?v=NMeBZlbs2dU&feature=related
http://www.youtube.com/watch?v=tMMrTRnFdI4&feature=related
http://www.youtube.com/watch?v=ZF2_ItzzVbs&feature=related
http://www.youtube.com/watch?v=NB7YfAvez3o&feature=related
http://www.youtube.com/watch?v=iGb93jCKVXs&feature=related
http://www.dnatube.com/video/1594/Protein-Modification-Golgi
http://www.youtube.com/watch?v=HpQLDBaHD_k&feature=related
http://www.youtube.com/watch?v=SGBiy1HlWH8&feature=related
http://www.youtube.com/watch?v=NSvAfwMEo7o
http://www.youtube.com/watch?v=OtyhPEyLhvA&feature=related
GMU Add/Drop Policy: As per GMU academic calendar.
Honor Code, Copyright, & Computing Policies: To promote a stronger sense of mutual
responsibility, respect, trust, and fairness among all members of the George Mason University
community and with the desire for greater academic and personal achievement, we, the student
members of the university community, have set forth this honor code: Student members of the George
Mason University community pledge not to cheat, plagiarize, steal, or lie in matters related to
academic work.
You are expected to adhere to all University policies and guidelines during your participation in this
course. All work must be your own. Inappropriate use of the work of others is a George Mason
University Honor Code violation. Please review the University’s website for information on the
following: Honor Code and Judicial Procedures; Copyright/Fair Use; and Responsible Use of
Computing.
If you are a student with a disability and you need academic accommodations please see me and
contact the Disability Resource Center (DRC) at 703.993.2474. All academic accommodations must
be arranged through that office. Students must inform the instructor at the beginning of the semester,
and the specific accommodation will be arranged through the Disability Resource Center.
Writing Center: Students who are in need of intensive help with grammar, structure or mechanics in
their writing should make use of the services of the Writing Center, located in Robinson A116 (703993-1200). The services of the Writing Center are available by appointment, online and,
occasionally, on a walk-in basis.
University Libraries “Ask a Librarian” http://library.gmu.edu/mudge/IM/IMRef.html