Original DNA composed of 4 bases
2. Thymine (In mRNA Uracil substituted)
DNA is transcribed by what to RNA?
What are your essential Amino Acids?
1. Cell differentiation correlates with loss of ability to ___________;
2. Highly specialized cells are what?
2. terminally differentiated
1. Terminally differentiated cells have a _______ life span,
2. and are replaced with new cells produced from where?
2. stem cells
_____ _____ are capable of self-renewal; cells divide without undergoing what?
1. Normal cell cycle is controlled by what?
2. What binds to surface receptors on the cell?
3. What relay signals into the cell?
1. Signal transduction
2. Growth factors
3. transmembrane proteins
What are the two types of growth factors?
1. Growth factors stimulate cell division
2. Growth-inhibiting factors inhibit cell division.
What are the cell cycle phases?
1. Healthy cells divide only when what favors cell division?
2. Cancer cells divide without what?
1. growth factor and growth-inhibiting factor balance favors cell division.
2. constraint (e.g., mutations in growth and growth-inhibiting factor genes).
1. All cancer cells contain what?
2. Two categories of cancer genes: dominant and recessive
1. Cancer cells contain genetically altered DNA
-Hereditary / Germline
-Somatic / Spontaneous
-dominant termed “proto-oncogenes”
-recessive termed “tumor suppressor”
1. Describe Gain-of-function mutations?
2. Describe loss-of-function mutations?
1. Gain-of-function mutations: altered or unregulated activity of a “proto-oncogene” leads to tumorigenesis
2. Loss-of-function mutations: loss of activity of tumor suppressors results in unregulated pathways and tumorigenesis
Hallmarks of Cancer?
1. Self-sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Evading apoptosis
4. Limitless reproductive potential
5. Capacity to invade other tissues
6. Sustained angiogenesis
7. Tissue invasion and metastases
8. Genomic instability
Cancer cells can invade by what?
Moecular basis of Cancer:
1. Mutations? 3
2. Which genes increase?
3. Which genes decrease?
4. What do these imblances lead to?
3. Tumor suppressor genes
4. Uncontrolled cell growth
1. What are Proto-oncogenes?
2. How do proto-oncogenes normally function? 3
3. What kind of cells can they be?3
1. Proto-oncogenes are normal cell proteins that have the potential to cause cancer when mutated
2. associated with cell growth, cell division and cell differentiation
3. can be:
-cell surface receptors
-enzymes - kinases/ phosphatases
Describe the following cancer types:
4. Germ cell tumors?
1. Carcinoma- epithelial cells
2. Sarcoma- connective tissue cells
3. Lymphoma and Leukemia
4. Germ cell tumors- Testicle and ovary
5. Blastomas- immature cells or embryonic tissue
Retinoblastoma (Rb) caused by what mutated gene?
Mutated Rb gene
Summary: Methods of identification of cancer critical genes?
1. Assay for oncogenic effects
2. Study of rare syndromes-tumor suppressors
3. Candidate genes
4. Genomics: exhaustive surveying is feasible. Identify every change in tumor cell vs. normal
Describe the steps in Carcinogenesis?
Describe the three types of progression in carcinogenesis?
1. Primary tumor growth
2. Local/Regional spread
3. Distant spread
Dividing cells are in what layer of the skin?
Describe the three steps in Invasion and metastasis?
A. Normal epithelium
B. Dysplasia (mutation)
C. Pre-malignant (Carcinoma in situ)
D. Malignant (Invasive Cancer)
What is pictured in the following?
Leukoplakia of the oral cavity: pre-malignant squamous mucosal change
What is the following?
Squamous cell carcinoma of the larynx
What is the following?
Apical lung mass in a 60 year old lady. Hx of ++ cigarettes and Marijuana.
1. Cancer cells grow into a clump and now needs what?
1. its own blood supply
Metastasis on a cellular level
Distant spread : Metastasis
Describe the kinds of spread?
1. Spread to other organs through the blood stream
2. Spread to other organs through the lymphatic fluid system
3. Seeding into spaces in the body
Sites of metastases of common cancers
Primary Brain? 2
Name the regional lymph node drainage in each of the following Primary Cancer Type:
1. Breast? 2
2. Lung? 3
3. Colorectal? 2
4. Prostate? 1
5. Melanoma? 1
Regional Nodal Drainage
5. Regional nodes
1. Describe local seeding?
2. What spaces for example? 3
1. Local seeding- The cancer has to start in, or invade into a body space.
1. Normal cell = 23 pairs of chromosomes = 46 = ______?
2. Cancer cell = Can have less than or more than
46 chromosomes =__________?
Describe the differentiation, characteristics, and growth rate of each of the following grades:
Cancer Stem Cell Theory
There are two competing visions of tumors.
Old cancer model? 3 steps
1) All tumor cells can form new tumors and are therefore equally tumorigenic.
2) Unregulated growth is due to serial acquisition of genetic events leading to the expression of genes that promote cell proliferation with concomitant silencing of growth inhibitory genes and blunting of cell death.
3) Cancer is a proliferative disease.
Cancer Stem Cell Theory
New Cancer Model?
1) Tumors arise from cells termed cancer stem cells that have properties of normal stem cells, particularly self-renewal and multipotent (a minority) of tumor cells.
2) Unregulated cell growth is due to a disruption in the regulatory mechanism in stem cell renewal.
3) Cancer is a stem cell disorder and not a simple mechanism whereby cell proliferation is disrupted.
Describe the difference in Cancer Stem Cell Therapy compared to Conventional cancer therapy?
1. Conventional chemotherapies kill what?
2. A population of cancer stem cells which gave rise to it, remains untouched and may cause what?
3. Development of specific therapies targeted at the ________ holds hope for improvement of survival and quality of life of cancer patients, especially for sufferers of metastatic disease
1. differentiated or differentiating cells, which form the bulk of the tumor but are unable to generate a new one.
2. a relapse of the disease.
3. stem cell
What are Cancer Stem Cells?
Cells that have properties of normal stem cells:
1) The abilities to self-renew.
2) The ability to differentiate into multiple cell types.
3) They form a distinct population in tumors that likely causes disease relapse and metastasis.
What are the surgical choices for breast cancer?
1. Lumpectomy + radiation
Describe the difference in sporadic versus hereditary cancers?
Patterns of Hereditary Cancers
1. More cancer (of related type) in a family than expected by chance alone
2. Vertical transmission within a family
3. Early ages of onset
4. Multiple primary cancers in one individual
Common Hereditary Cancer Syndromes
1. Hereditary Breast/Ovarian cancer syndrome
2. Lynch (HNPCC) syndrome
3. Familial Adenomatous polyposis syndrome
Which does each of the following affect and what genes are mutated:
1. Hereditary Breast/Ovarian cancer syndrome? 5 organs, 2 genes
2. Lynch (HNPCC) syndrome? 7 organs, 5 genes
3. Familial Adenomatous polyposis syndrome? 6 organs, 2 genes
1. Breast, ovarian, male breast, prostate, pancreatic
2. Caused by mutations to BRCA1 or BRCA2 genes
1. Colon, gastric, endometrial, ovarian, small bowel, pancreas, brain
2. Caused by mutations to MLH1, MSH2, MSH6, PMS1, PMS2 genes
1. Colon, stomach, thyroid, brain, liver, adrenal gland
2. Caused by mutations to APC or MYH genes
1. What is lynch syndrome?
2. Which genes are involved? 5
3. Malignancies may include what? 7
1. Mismatch repair genes: maintain DNA integrity during DNA replication
-Often leads to microsatellite instability in tumors
2. Mutations to 5 different genes (genetic heterogeneity)
-MLH1, MSH2, MSH6, PMS1, PMS2
3. colon, stomach, uterine, small bowel, ovarian, ureters, kidney
1. Prophylactic Surgery Options for HNPCC-Associated Mutation Carriers
2. Surgery does not do what?
1. Options include
2. Surgery does not eliminate cancer risk
Expert panel made no recommendation for or against surgery due to unproven efficacy*
Surveillance Options for Pts
of HNPCC-Assoc. Mutations
1. Colorectal Cancer intervention?
3. Endometrial cancer intervention? 2
1. Li-Fraumeni Syndrome (P53 gene)- which cancers? 5
2. Cowden Syndrome (PTEN gene)? 5
3. Peutz-Jeghers syndrome (STK11 gene)? 5
4. Xeroderma pigmentosa syndrome (XP3 gene)? 3
5. Von Hippel-Lindau syndrome (VHL gene) 5
6. Multiple endocrine neoplasia-1 syndrome (MEN1 gene)? 4
1. Breast, bone, leukemia, brain, soft tissue sarcomas
2. Breast, uterine, thyroid, ovarian, colon cancers
3. Colon, small bowel, breast, ovarian, pancreatic cancers
4. Basal cell, squamous cell and melanoma cancers
5. Brain, retina, kidney, pancreas, adrenal gland cancers
6. Pancreas, pituitary, parathyroid, thyroid cancers