Molecular biology of cancer

Question 1

What is Neoplasia?

Answer 1

Tumour growth

Question 2

What is Neoplasm ?

Answer 2

Tumour

Question 3

What is adenocarcinoma

Answer 3

a malignant tumour of glandular epithelium

Question 4

What is adenoma ?

Answer 4

a solid, benign glandular tumour

Question 5

What is anaplasia?

Answer 5

loss of differentiated charachteristics

Question 6

What is aneuploidy?

Answer 6

presence of extra chromosome

Question 7

What is angiogenesis?

Answer 7

new growth of blood vessels

Question 8

What is a benign tumour?

Answer 8

a tumour that does not invade or metastasize

Question 9

What is a carcinoma ?

Answer 9

malignant tumour of epithelium

Question 10

What is hyperplasia?

Answer 10

increase in number of cells in response to stimulus

Question 11

What is Leukemia ?

Answer 11

malignant disease of blood forming organs leading to over production of neoplastic white blood cells

Question 12

What is lymphoma ?

Answer 12

solid tumour of T or B lymphocytes e.g. in lymph nodes, thymus or spleen

Question 13

What is a malignant tumour?

Answer 13

tumour that is capable of invading surrounding tissues and of metastasizing

Question 14

What is metaplasia?

Answer 14

abnormal alternation in the structure of cells

Question 15

What is metastasis?

Answer 15

a secondary tumour arising from cells carried to a distant site from a primary tumour

Question 16

What is a myeloma ?

Answer 16

a plasma cell tumour

Question 17

What is an oncogene?

Answer 17

a gene causing cancer

Question 18

What is a proto-oncogene?

Answer 18

the normal cellular counterpart of an oncogene

Question 19

What is a sarcoma?

Answer 19

a malignant tumor of mesenchyme (connective tissue)

Question 20

What is a transformation?

Answer 20

in the context of cancer means a change of morphological appearance of a cell

Question 21

What is a tumour suppressor gene?

Answer 21

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.

Question 22

What is Cancer?

Answer 22

Uncontrolled cell Division and Uncontrolled cell Survival - in cancer cells there is loss of control of both the division /differentiation process and apoptosis.

Question 23

What statistics do you know about cancer?

Answer 23

• 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.

Question 24

How many forms of cancer are there?

Answer 24

• 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

Question 25

Other origins of cancer cells?

Answer 25

1% - from connective tissue(sarcomas )- 8% - from haemapoetic cells (lymphomas, leukaemias )

Question 26

different cancer types have very different prognosis? ( give examples)

Answer 26

e.g. cancer of the lip -99% survivalcancer of lung - 8% survival

Question 27

Factors that control survival time?

Answer 27

early diagnosis - lack of spread to other sites- response to treatment - quality of care

Question 28

What is the Molecular basis of cancer?

Answer 28

• 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

Question 29

Why is it said that cancer is a multistep process?

Answer 29

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

Question 30

What are the stages in tumour development?

Answer 30

1. 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!)

Question 31

What are some charachteristics of tumours?

Answer 31

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

Question 32

What is the genetic basis of human cancer?

Answer 32

-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

Question 33

What do we know about tumour supressor genes?

Answer 33

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.

Question 34

What are some examples of tumour suppressor genes?

Answer 34

• 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

Question 35

What is the relationship between mutations and cancer?

Answer 35

• 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.

Question 36

Give some examples of oncogenes?

Answer 36

mutant growth factor receptors- single cascade components- transcription factors- cell-cell components - anti- apoptotic factors

Question 37

What are chromosomal translocations?

Answer 37

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.

Question 38

What is Gene Amplication?

Answer 38

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.

Question 39

What is gene sequencing?

Answer 39

• Human genome sequence ‘ complete’- cancer genome sequencing project- use of next generation sequencing - exosome sequencing

Question 40

What is hypoxia’s role in tumour development?

Answer 40

the tumour cells are often exposed to low oxygen, hypoxia or inflammation

Question 41

What are cancer cell migration steps ( 5 steps !)?

Answer 41

1. escape from the tumour 2. invasion of vascular system3. movement through the blood stream4. homing to distant organs5. attachment 6. invasion

Question 42

What is cancer therapy ?

Answer 42

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.