Cancer Biology

Question 1

neoplasm definition

Answer 1

a new and abnormal growth resulting from autonomous cell division

Question 2

benign definition

Answer 2

grow slowly and remain localised to the site of origin

Question 3

malignant definition

Answer 3

invade and spread to different site

Question 4

metastasis definition

Answer 4

multi-step process by which tumour cells move from a primary site to colonise a secondary site

Question 5

tumorigenesis process

Answer 5

uncontrolled cell proliferation
increased growth capability
blocked differentiation
increased cell motility
acquired tissue invasion capability
loss of genomic stability

Question 6

6 features that cancer cells will acquire

Answer 6

1- self-sufficiency in growth signals: autonomous drive to proliferate (Ras, bcr-abl, HER-2)
2- insensitivity to growth-inhibitory signals: inactivation of tumour suppressor genes that normally inhibit growth (RB)
3- evasion of apoptosis: suppress and inactivate genes and pathways that normally able cells to die (p53, bcl-2)
4- limitless replication potential: activate specific gene pathways that render them immortal even after generation of growth (telomerase)
5- sustained angiogenesis: acquire the capacity to draw out their own supply of blood and blood vessels (VEGF)
6- Tissue invasion and metastasis: acquire the capacity to migrate to other organs, invade other tissues and colonise these organs (cadherin, proteases)

Question 7

oncogene definition

Answer 7

a gene which in certain circumstances can transform a cell into a tumour cell

Question 8

mutations available of proto-oncogene

Answer 8

deletion/point mutation
regulatory mutation
gene amplification
chromosome rearrangement

Question 9

process of tumerigenisis

Answer 9

uncontrolled cell proliferation
increased growth capacity
blocked differentiation
increased cell motility
acquired tissue invasion capability
loss of genomic stability

Question 10

protooncogenes definition

Answer 10

a normal cellular gene that encodes a protein usually involved in cell growth and proliferation

Question 11

tumour suppressor gene definition

Answer 11

a gene whose encoded protein directly or indirectly inhibits progression through the cell cycle and in which a loss-of-function mutation is oncogenic

Question 12

example of a protooncogene

Answer 12

Ras

Question 13

example of a tumour suppressor gene

Answer 13

RB

Question 14

what is Ras

Answer 14

a GTPase that transduces signals from CSRs

Question 15

mutation of Ras

Answer 15

points mutations -> hyperactive Ras that is ‘on’ all the time (dominant effect)
30% of all tumours screened carry mutation from CSRs

Question 16

what is BRAF

Answer 16

kinase that transduces signals from CSRs

Question 17

mutation of BRAF

Answer 17

point mutations -> hyperactive kinase activity that is ‘on’ all the time (dominant effect)
>50% all melanomas have a mutated BRAF

Question 18

what is EGFR

Answer 18

CSR that recieves a extracellular signals

Question 19

mutation of EGFR

Answer 19

deletion of extracellular portion
-> absence of EGF (dominant effect)
non-small cancer

Question 20

Bcr gene on chr 22 + abl gene on chr 9

Answer 20

bcr-abl hybrid gene in Chronic Myeloid Leukaemia (CML)
philadelphia translocation

Question 21

what is ERB B2

Answer 21

transmembrane receptor that receives signals from other cells

Question 22

mutations of ERB B2

Answer 22

amplified in 20% of breast cancers -> poor prognosis

Question 23

how does RB oncogene activation lead to cancer

Answer 23

2 hit hypothesis
two mutational events must occur at the same locus to result in tumorigenesis
leads to: retinoblastomas, sarcomas, bladder/ breast/ lung carcinomas

Question 24

how does p53 oncogene activation lead to cancer

Answer 24

tetrameric transcription factor - dominant negative
germ-like mutation predispose to Li-Fraumeni Syndrome
inactivated in 50% all human cancers

Question 25

briefly describe the molecular changes that allow a tumour to metastisise

Answer 25

cells in primary tumour must be able to; break free, invade BM and the surrounding stroma (+out of circulation again) and then proliferate in a new area of the body
epithelial tumours often lose E-cadherin (adherens junction) partially or completely as they progress toward malignancy
altered integrin expression is associate with types of cancers
proteases - MMP-8
- degrades collagen IV so that it is easier for the cells to penetrate the BM