Molecular Biology of Cancer Flashcards
What is Neoplasia?
Tumour growth
What is Neoplasm ?
Tumour
What is adenocarcinoma
a malignant tumour of glandular epithelium
What is adenoma ?
-a solid, benign glandular tumour
What is anaplasia?
loss of differentiated charachteristics
What is aneuploidy?
presence of extra chromosome
What is angiogenesis?
new growth of blood vessels
What is a benign tumour?
-a tumour that does not invade or metastasize
What is a carcinoma ?
- malignant tumour of epithelium
What is hyperplasia?
increase in number of cells in response to stimulus
What is Leukemia ?
-malignant disease of blood forming organs leading to over production of neoplastic white blood cells
What is lymphoma ?
- solid tumour of T or B lymphocytes e.g. in lymph nodes, thymus or spleen
What is a malignant tumour?
-tumour that is capable of invading surrounding tissues and of metastasizing
What is metaplasia?
-abnormal alternation in the structure of cells
What is metastasis?
-a secondary tumour arising from cells carried to a distant site from a primary tumour
What is a myeloma ?
a plasma cell tumour
What is an oncogene?
-a gene causing cancer
What is a proto-oncogene?
-the normal cellular counterpart of an oncogene
What is a sarcoma?
a malignant tumor of mesenchyme (connective tissue)
What is a transformation?
-in the context of cancer means a change of morphological appearance of a cell
What is a tumour suppressor gene?
-genes whose normal role is to regulate cell division in a negative fashion ( leading to cell growth arrest) and following mutation or loss of one or both alleles , may have the effect of allowing cells to progress through cell division in an unrestricted fashion.
What is Cancer?
Uncontrolled cell Division and Uncontrolled cell Survival
- in cancer cells there is loss of control of both the division /differentiation process and apoptosis.
What statistics do you know about cancer?
- 1 in 3 people will suffer from cancer in their life
- 1 in 4 deaths due to cancer
- 6 million new cases every year worldwide.
How many forms of cancer are there?
- more than 200 different forms of cancer
- they differ according to the cell type from which they derive.
- 85% are epithelial origin called carcinomas
- these cells form the barrier layer exposed to ‘carcinogens’ in the environment
- skin cancers are ‘ basal cell carcinoma ‘ ,
- lung cancers are ‘ adenocarcinoma ‘
- colon cancers are ‘ colorectus carcinoma’
Other origins of cancer cells?
-1% - from connective tissue
(sarcomas )
- 8% - from haemapoetic cells
(lymphomas, leukaemias )
different cancer types have very different prognosis? ( give examples)
e.g.
cancer of the lip -99% survival
cancer of lung - 8% survival
Factors that control survival time?
- early diagnosis
- lack of spread to other sites
- response to treatment
- quality of care
What is the Molecular basis of cancer?
- mutations in the DNA that codes for genes whose products are normally involved in the control of division, differentiation and cell survival
- most mutations are somatic !
- some are inherited !
- this has lead to great insights into normal growth and development
Why is it said that cancer is a multistep process?
- because many unlikely mutations must accumulate in one cell
- mutations that affect genetic stability are of especial importance
-these mutations allow new variants to arise more quickly - cancer cells are genetically unstable
which allows rapid evolution - therefore allowing drug resistance
What are the stages in tumour development?
- mild dysplasia (25-30 divisions)
- severe dysplasia (100 million cells visible on xray)
- carcinoma in situ (1000 million cells tumour is palpable )
- invasive carcinoma - (tumour breaks through basement membrane )
- malignant metastasis ( 1,000,000 million cels tumour throughout body and organs - death!)
What are some charachteristics of tumours?
- avoiding immune response
- tumour promoting inflammation
- deregulating cellular energetics
- genome instability and mutation
- the tumour microenvironment is very different from normal tissues.
- the tumour cells have adapted a glycotic metabolism
What is the genetic basis of human cancer?
- activation of genes by mutation that promote cell proliferation and cell survival
- dominant gain of function mutations
- protooncogene mutates to oncogene
- regulated growth signal /survival signal ==== mutation === unregulated growth signal / survival signal
- inactivation of genes by mutation that normally limit cell proliferation and cell survival
- recessive loss of function mutations
- tumour supresser gene ==== mutations ==== mutant tumour supressor gene
What do we know about tumour supressor genes?
- because loss of function mutation need to lose both parental copies for affect to be seen
- if you inherit a germ line mutation in one you are at a greater risk of developing cancer.
What are some examples of tumour suppressor genes?
- p53 gene - mutant in more than 50% of human cancerss
- part of cells checkpoint repsonse to DNA damage
- retinoblastaoma gene - mutant in all retinoblastomas but also lung and other cancers.
- key negative regulator of the transcription of genes needed for cell cycle.
-adenomatous polypossis coli gene (APC) mutant in most colorectal cancers at early stage in disease. involved in chromosome stability
HmutS gene - mutant in some forms of colorectal cancer - mutations cause a defect in DNA mismatch repair
What is the relationship between mutations and cancer?
- since somativ mutation of DNA underlies cancer development it is thought that:
- mutagens are carcinogens
- cancer is avoidable if mutagen exposure can be reduced.
- mutagen testing can help identify cancer causing agents in the environment.
Give some examples of oncogenes?
- mutant growth factor receptors
- single cascade components
- transcription factors
- cell-cell components
- anti- apoptotic factors
What are chromosomal translocations?
it is found that in cancer there is chromosomal instability
- tumours are aneuploid ( incorrect number - triploid, haploid )
- tumours have many brokem and rearranged chromosomes clearly seen using FISH and CGH techniques
= careful cytology on leukaemias showed certain common very conserved events.
What is Gene Amplication?
- cytological examination of tumours shows double minute chromosomes
- cytological examination of tumours shows HSRs homogenously staining regions
- both contain multiple copies of same Chromosomal fragment.
What is gene sequencing?
- Human genome sequence ‘ complete’
- cancer genome sequencing project
- use of next generation sequencing
- exosome sequencing
What is hypoxia’s role in tumour development?
- the tumour cells are often exposed to low oxygen, hypoxia or inflammation
What are cancer cell migration steps ( 5 steps !)?
- escape from the tumour
- invasion of vascular system
- movement through the blood stream
- homing to distant organs
- attachment
- invasion
What is cancer therapy ?
- understand the genetic defect
- find the achillies heel of the cancer
- block new blood vessel formation
- change the microenvironment
- target on mutant cells
- personalised cancer treatment.
