Cancer Genetics Flashcards
What is cancer
All cancers are genetic diseases and changes in the DNA sequence of key genes which are known as cancer genes cause this abnormal division of the cells .
DNA polymerase can also make mistakes , changes can also occur due to exposure to mutagens such as UV
What causes cancer
Chemicals ( e.g. from smoking) and radiation can damage genes ( environment)
Viruses can introduce their own genes into cells ( exogenous factors)
By heredity , alteration in genes that make a person more susceptible to cancer can be passed to the next generation ( genetics - rate and common)
Meat cooked at high temps can also lead to an increased risk of cholesterol, pancreatic and prostate cancer
What is a benign tumour
Massive well differentiated cells that grow slowly and is capsulated and lack the ability to invade neighbouring tissues or to metastasise
What is a malignant tumour
Not limited in its growth and the cells are poorly differentiated and capable of dividing into adjacent issues and maybe capable of spreading distant issues at a microscopic level if there are new bed vessels it may be categorised as malignant
What do cancer cells look like
Large number of dividing cells Large, variably shaped nuclei Large nucleus to cytoplasm ratio Variation in size and shape Loss of normal cell features Disorganised arrangement Poorly defined tumour boundary
Microscopic appearance of cancer cells
Pronounced irregular microscopic membrane and there are increased activity of nucleoporins which causes an increase in the input of transcriptional factor
Carcinoma
Rise from epithelial cells - most common are lung, breast and colon
Sarcoma
Elle found in the supportive cells of the body . Bone, cartilage, fat connective tissue and muscle
Lymphomas
Cancers that arise in the lymph nodes and tissues of the body’s immune system
Leukemia
Cancers of cells that grow in the bone marrow and accumulate in the bloodstream
Cancers affecting children
Leukaemia s ( ALL) and in tissues which are undergoing a high rate of proliferation such as brain and testicular cancer
6 hallmarks of cancer
Self sufficiency in growth signals Evading apoptosis Insensitivity to anti growth signals Sustained angiogenesis Tissue invasion and metastasis Limitless replication potential
( also deregulated metabolism and avoid immune destruction has been added)
The life time risk of developing cancer is a particular tissue is correlated with how often stem cells in the tissue divide
So intestine has high cell proliferation rate and so increased risk of cancer
Germ.one mutations
Present in egg or sperm cell
Are heritable ( family syndrome)
Rare
Germ line cells are the only cells that can undergo mitosis and meiosis
Somatic mutations
Occur in non germ line tissues
Are non heritable
Very common ( 90% of all cancers)
Diff types of mutations in cancer cells
Deletions Duplications Inversions Translocations Single base substitutions ( point mutations- silent, nonsense and missense ) Chromosomal instability Aneuploidy
Multi step carcinogens is with tumour cells as an example
1) initiation where thee is irreversible genetic mutations and allows excessive cell prolif . Colon cancer starts with defect in tumour suppressor gene ( APC)
Then more mutations occur in DNA repair genes or other tumour suppressor genes ( p53) and other growth related genes ( K-Ras)
2) tumour becomes cancerous
3) over time accumulated damage can yield a highly malignant , metastatic tumour
Example of distinct somatic mutations
Some cancers have distinct somatic mutations ( C>T) . The DNA damage from UV radiation leads to the formation of covalent bonds between two adjacent pyrimidines ( C and T) in the DNA molecule
Or in smokers - G to T transition
Passenger mutations
Many mutations can be tolerated by somatic cells and have no effect but may be in the same genome where a driver mutation is located ( known as hatch hiking)
Driver mutation
Leads to clinal expansion - may be in p53 and tumour suppressor
Passenger vs driver mutation
Driver mutation will have greater effect on protein function than passenger mutation
And will have more frequent mutations than background mutation rate in a gene
But hard to determine as there is so much variation
Oncogenes
Gene that has the potential to cause cancer and it regulates cell proliferation, differentiation and and apoptosis , one mutations is sufficient for role in cancer development ( dominant / gain of function )
What is a tumour suppressor gene
Regulates cell during cell division and mutation - might be more important in progression of cancers than the proto oncogenes ( recessive/ loss of function )
