10 Questions
Which gene's mutations initiate the formation of adenomas?
APC
What is the outcome of mutations in the DNA mismatch repair system?
Speeding up of the cancer development process
What is the role of growth factors in cancer development?
They produce their effects by interacting with specific receptors on cell surfaces
Which genes are associated with cancer development in patients with hereditary nonpolyposis colon cancer?
APC, BRAF, K-RAS
What is the outcome of instability of chromosomes and microsatellites in many tumors?
It likely involves mutations in a considerable number of genes
What is the role of oncogenes in cancer development?
They promote tumor growth
Which genes are involved in the development of colorectal cancers?
A sequence of mutations in oncogenes and tumor suppressor genes
What is the OMIM number associated with familial adenomatous polyposis?
175100
What is the outcome of mutations in the APC gene?
Initiation of adenoma formation
What is the role of tumor suppressor genes in cancer development?
They suppress tumor growth
Study Notes
Epigenetic Changes in Gene Expression
- Many protein and DNA modifications are potentially reversible.
- Inhibitors of DNA methyltransferases (DNMTs) include 5-azadeoxycytidine and decitabine.
- Inhibitors of histone deacetylases (HDACs) include valproic acid and vorinostat.
- These agents have been used to treat certain types of leukemias and lymphomas.
Tumor Angiogenesis
- Tumor cells need an adequate blood supply to survive.
- Tumor cells and surrounding cells secrete angiogenic factors to stimulate new blood vessel growth.
- Hypoxia induces HIF-1, which increases levels of vascular endothelial growth factor (VEGF).
- VEGF proteins interact with specific tyrosine kinase receptors on endothelial and lymphatic cells.
MicroRNAs in Cancer
- Oncogenic microRNAs include miR-17-92, miR-21, and miR-155.
- Tumor suppression microRNAs include let-7, miR-34, miR-15, and miR-16.
- MicroRNAs influence extrinsic factors that modulate tumors, such as interactions with the immune system and stromal cells.
- MicroRNAs are being investigated as biomarkers for cancer diagnosis, prognosis, and classification.
- MicroRNAs hold promise in therapy, where oligonucleotides are used to enhance expression of tumor suppressor miRNAs or antisense oligonucleotides are used to counter the action of oncogenic miRNAs.
Development of Colorectal Cancers
- Multistep genetic changes are associated with the development of colorectal cancers.
- Mutations in the APC gene initiate the formation of adenomas.
- A sequence of mutations in oncogenes and tumor suppressor genes can result in further progression to large adenomas and cancer.
- Patients with familial adenomatous polyposis (FAP) inherit mutations in the APC gene and develop numerous dysplastic aberrant crypt foci (ACF).
- Tumors from patients with hereditary nonpolyposis colon cancer (HNPCC) go through a similar series of mutations.
Growth Factors and Cancer Development
- Growth factors produce their effects by interacting with specific receptors on cell surfaces.
- Growth factors initiate various signaling events.
- Abnormalities of growth factors and their receptors play a major role in cancer development.
- Oncogenes involved in cancer development include K-RAS, BRAF, and PI3KCA.
Learn about the role of epigenetic changes in gene expression and cancer treatment. Discover how inhibitors of DNA methyltransferases and histone deacetylases can be used to treat certain types of leukemia. Test your knowledge on the reversible nature of these modifications.
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