Cellular & molecular biology of cancer Flashcards
what is the difference between malignant and benign tumours
- Benign = Locally confined in non-vital organ, Differentiated
- Malignant = Invades other tissues, Spreads to distinct organ via the blood and lymphatic system, Loss of differentiated morphology
What is the evidence for the genetic basis of cancer
- loss of growth control is heritable (somatic)
- DNA damaging agents are generally carcinogenic
- DNA repair deficiency syndromes are associated with an increased susceptibility to carcinogens
- Genetic predisposition to some cancers is hereditary
What evidence shows loss of growth control is heritable
In vitro growth of tumour cells and transplantable tumour lines suggest genetic alteration are involved
what evidence shows that DNA repair deficiency syndromes are associated with an increased susceptibility to carcinogens
Ataxia telangiectasia
Xeroderma pigmentosum
HNPCC (hereditary non-polyposis coli) - DNA mismatch repair defect
what evidence shows that DNA damaging agents are generally carcinogenic
Experimental and Epidemiological evidence
Occupation and lifestyle:
□ Ionising radiation – leukaemia and osteosarcoma
□ Ultra violet light – skin cancers, including melanoma
□ Cigarette smoking – lung cancer, bladder cance
What is the evidence shows that genetic predisposition to some cancers is hereditary
Retinoblastoma, Wilm’s tumour, familial adenomatous polyposis, HNPCC, multiple endocrine neoplasia (MEN), Li Fraumeni, BRCA1&2, acoustic neuroma, etc.
what is the clonal origin of tumours
○ X-linked G6PD markers A and B, distinguishable by electrophoretic mobility
○ Random X-inactivation post fertilisation in females generates a mosaic in normal tissues
○ Tumours are found to express only one of the alleles whereas the surrounding normal tissue is a mosaic
Animals leukaemia, lymphomas and sarcomas can be caused be
Viruses
Rare transmissible
Cancer is not normally infectious though
What are the three main groups that tumours causesing viruses can be classified
- DNA viruses
- Long latency retroviruses
- Acutely transforming retroviruses
what provided the first evidence for the existence of specific cancer causing genes
Acutely transforming retroviruses
The majority of common sporadic cancers in humans includes. These do not have a pattern of _
- Most leukaemias, lung, colorectal, breast, & bladder cancer
- incidence that would suggest a transmissible viral cause
Describe the different types of tumour viruses
DNA - viruses with a DNA genome (Sarcoma)
RNA - Viruses with an RNA genome, also known as retroviruses because their RNA has to be copied into DNA before the protein encoded by the viral genes can be expressed in the host (cervical cancer)
ATR - Acutely transforming retroviruses are so called because the cancers arising from them manifest themselves particularly rapidly (only in animals)
How do in vitro transformation assays aid in identifying cancer biology
- Characteristics of in vitro transformation: Disordered colony morphology, Loss of contact inhibition, Anchorage independent cell growth
- Speed and efficiency suggested direct action of a viral gene
- The viruses found to encode only 3 or 4 genes
- This brought the genetic mechanisms of cancer within reach and laid the foundations of our current concepts of the molecular genetic basis of cancer
Describe how the rous sarcoma virus lead to the discovery of the src oncogene
- A single gene encoding a small protein found to profoundly alter the growth pattern of infected cells and render them cancerous
- Because of the association with sarcomas the gene was called src (pronounced “sark”)
- Term oncogene coined to categorise genes such as src that can transform cells and cause cancer
What implied that there is many alternative ways in which the growth of a cell can be deregulated to give rise to cancers
Different viruses were found to carry different oncogenes, with products located in different parts of the transformed host cell and exhibiting a range of different biochemical functions
