Genetic predisposition to Cancer Flashcards
Describe the differences between somatic mutations and germline mutations
Somatic mutations o Occur in non-germline tissues o Are non-heritable Germ line mutations e.g. in sperm or ovum o Present in egg or sperm o Are heritable o Cause cancer family syndromes o Causes all cells in offspring to be effected
Define the important of clonal expansion in the formation of neoplasms
Cells in neoplasms compete for resources, such as oxygen and glucose, as well as space. Thus, a cell that acquires a mutation that increases its fitness will generate more daughter cells than competitor cells that lack that mutation. In this way, a population of mutant cells, called a clone, can expand in the neoplasm. Clonal expansion is the signature of natural selection in cancer.
What are the 3 major genetic mutations associated with cancer development?
- Oncogenes
- Tumour suppressor genes
- DNA damage-response genes
What are proto-oncogenes?
Proto-oncogenes – normal gene that codes for proteins that regulate cell growth and differentiation
Mutations can change a proto-oncogene into an oncogene. Oncogenes can accelerate cell division and play a role in cancer development
What are oncogenes?
Mutated proto-oncogenes, allowing the cells to carry through cell division unchecked.
What are tumour suppressor genes?
A tumor suppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. The loss of these genes may be even more important than proto-oncogene/oncogene activation for the formation of many kinds of human cancer cells
What are the DNA damage response genes?
The DNA damage gene response involves a network of cellular pathways that sense, signal and repair DNA lesions. Surveillance proteins that monitor DNA integrity can activate cell cycle checkpoints and DNA repair pathways in response to DNA damage, to prevent the generation of potentially deleterious mutations.
What is mismatch repair?
DNA mismatch repair is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage. Mismatch repair is strand-specific.
What cancer is associated with errors in mismatch repair?
HNPCC – hereditary non-polyposis colorectal cancer
What does mismatch repair usually result in?
Microsatellite instability
What is microsatellite instability?
Microsatellite instability (MSI) is the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR). The presence of MSI represents phenotypic evidence that MMR is not functioning normally.
Define a benign tumour
Benign – lacks ability to metastasize. Rarely or never become cancerous. Can still cause negative health effects due to pressure on other organs.
Define a dysplastic tumour
Dysplastic – ‘benign’ but could progress to malignancy. Cells show abnormalities of appearance & cell maturation. Sometimes referred to as ‘pre-malignant’ e.g. bowel polyps
Define a malignant tumour
Malignant – not ‘benign’. Able to metastasize.
Give an example of a cancer inherited dominantly due to a mutation to a proto-oncogene
MEN2 (multiple endocrine neoplasia)
