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 ‘ b
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% survivalcancer 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 de
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 unstablewhich allows rapid evolution - therefore allowing drug resistance
What are the stages in tumour development?
- mild dysplasia (25-30 divisions)2. severe dysplasia (100 million cells visible on xray)3. carcinoma in situ (1000 million cells tumour is palpable )4. invasive carcinoma - (tumour breaks through basement membrane )5. 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 si
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 fo
What is the relationship between mutations and cancer?
- since somativ mutation of DNA underlies cancer development it is thought that:1. mutagens are carcinogens2. cancer is avoidable if mutagen exposure can be reduced.3. 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 2. invasion of vascular system3. movement through the blood stream4. homing to distant organs5. attachment 6. 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.
