Cancer traits 1

Question 1

Cancer is a disease of what?

Answer 1

genome

Question 2

What do carcinogens do?

Answer 2

produce mutations

Question 3

What do mutations in somatic cells cause?

Answer 3

transformation and carcinogenesis

Question 4

What is initiation

Answer 4

initiation of cancer development is clonal
- mutation in one specific cell will give a rise to whole tumour

Question 5

What is carcinogenesis?

Answer 5

normal cells transformed into cancerous cells

Question 6

What is the process of tumour cells

Answer 6

continue accumulating mutations, can evolve -> sub-clonal selection offers growth advantage and explains cell heterogeneity in tumours
- cells get different mutations
mutations in germ cells can be inherited increasing cancer risk but rarely causing it immediately

Question 7

What are the names if cells in processing to malignant tumour?

Answer 7

normal cell (initiation occurs)->initiated cell (promotion occurs)-> preneoplastic cell (progression occurs) -> neoplastic cell (metastasis occurs)-> malignant tumour

Question 8

What is an abnormal cell cycle?

Answer 8

unreplicated, mutated or damaged DNA, blocks progression of cell cycle at checkpoints

Question 9

What is the process of abnormal cell cycle?

Answer 9

initial mutation inactivates a negative cell cycle regulator -> next mutation over activates a positive cell cycle regulator -> third mutation inactivates a genome stability factor->additional mutations accumulate rapidly->cancer cell

Question 9

What is the difference between a normal cell and a cancer cell during DNA damage?

Answer 9

normal cell will lead to apoptosis whereas cancer cell will continue dividing

Question 10

What is missense mutation?

Answer 10

change of single DNA base resulting in change in amino acid sequence & change of protein function

Question 11

What is frameshift mutation

Answer 11

addition or removal of DNA bases shift DNA & amino acid sequence; results in different protein

Question 12

what is nonsense mutation

Answer 12

change of single DNA base creates stop codon that terminates translation; results in shorter protein with no or abnormal function

Question 13

what are chromosome rearrangements?

Answer 13

piece of chromosome breaks & is lost entirely (deletion), moves to different location (translocation), flips direction (inversion), or is repeated (duplication)
Can alter several genes at once, generating fusion genes

Question 14

What is proto-oncogenes

Answer 14

normal cellular genes which regulate cell growth &/or division & differentiation

Question 14

What is an oncogene

Answer 14

a proto-oncogene that has been activated by mutation or over expression - results in deregulated cell division

Question 15

what are the sequences of stop codon in mRNA

Answer 15

UAA, UAG, UGA

Question 16

What are the features of sense DNA

Answer 16

DNA is responsible for storing & transferring genetic information
One strand of DNA is called the sense strand because when you read it in the right direction, it provides the code to make a protein
The sense strand is bonded to an opposite DNA strand that is called the antisense/noncoding strand
Antisense doesn’t carry the translatable code, but serves as a template during transcription

Question 16

What are the stop codon sequences in sense DNA

Answer 16

TAG, TGA, TAA

Question 17

What is HER2 + function

Answer 17

encodes human epidermal growth factor receptor 2, has tyrosine kinase activity

= breast cancer

Question 17

What is the cause of oncogene activation

Answer 17

1. gene mutation: results in different oncoprotein than normal protein
   - point mutations: in proto-oncogene or in promoter/regulatory element
   - chromosomal translocation: fusion in proteins or disruption of regulatory elements
2. oncoprotein are same as normal protein but overexpressed
   - gene amplification

one alteration in one copy of protocol-oncogene is enough to convert it into an oncogene
proto-oncogene mutation mainly affect somatic cells

Question 17

What are the examples of oncogenes?

Answer 17

HER2
KRAS
BCR-ABL1
MYC

Question 18

What is KRAS + function

Answer 18

GTPase (converts GTP->GDP)protein involved in signal transduction, controls cell growth and differentiation downstream of receptor tyrosine kinases, point mutation -> protein permanently active -> continuous proliferation

=lung cancer

Question 19

what is BCR-ABL1 + Function?

Answer 19

philadelphia chromosome: fusion protein due to reciprocal chromosomal translocation between chromosomes 9 & 22
- has consituitave (unregulated) tyrosine kinase activity

=chronic myeloid leukemia

Question 20

What is MYC and function?

Answer 20

family of photo-oncogenes that code for transcription factors - pathogenic alterations in MYC involved activation, amplifications and translocations = lymphoma (c-MYC) = neuroblastoma (n-MYC)

Question 21

TSG function ?

Answer 21

-Encode proteins that maintain cell cycle checkpoints & control genome stability -Inhibit replication & proliferation of damaged cells by: -Repair of DNA damage (e.g. BRCA1/2) -Apoptosis (TP53)

Question 22

What happens if TSG is inactivated?

Answer 22

Knudson's 2-hit hypothesis: loss of function mutations in TSG are recessive in nature--> one normal allele is sufficient for cellular control "Second hit" affecting normal allele--> disrupts gene function Familial (heritable) cancers develop after additional loss of normal functional allele (loss of heterozygosity)

Question 23

What is heterozygous state?

Answer 23

indicates absence of a functional TSG copy - but people remain healthy as there is still one functional gene left on the other chromosome of the pair - the other copy can be inactivated by point mutation or other mechanisms -> results in loss of heterozygosity event and leaving no TSG to protect the body loss of heterozygosity doesn't imply a homozygous state (which would require presence of 2 identical alleles in the cell)

Question 24

What is TP53 + function?

Answer 24

a TSG example - codes for tumour protein p53 - detects cellular stress (DNA damage) -> cell cycle arrest -> damage repair or apoptosis - over 50% of dancer contain TP53 gene mutations (missense)

Question 25

What is Li-fraumeni syndrome

Answer 25

people who inherit only one functional tp53 allele -> most likely will develop cancer

Question 26

What is RB1 + function?

Answer 26

- example of TSG - codes for RB (retinoblastoma) protein - prevents cell growth by inhibiting cell cycle - when cells are ready to divide, RB is phosphorylated (inactivation) -> cell cycle progresses - RB mutation, gene deletion or loss of heterozygosity lead to retinoblastoma (eye cancer) -> affects young children 40% germinal, 60% non

Question 26

What occurs if there are mutation in DNA repair gene?

Answer 26

accumulation of mutation -> genomic instability, activation of oncogenes and loss of tumour supressors

Question 27

What is BRCA and

Answer 27

an example of DNA repair gene -BRCA1/2 inherited mutations increase risk of breast, prostate, ovarian cancers

Question 28

sustaining proliferative signalling in normal cells?

Answer 28

require growth factors to proliferate - GF bind to cell-surface receptors, typically with intracellular tyrosine kinase domains TKDs send intracellular signals regulating - cell cycle progression - cell growth - cell survival - energy metabolism

Question 28

What occurs in cancer cells in proliferative signalling

Answer 28

synthesise of GF's/ligands -> autocrine proliferative signalling (positive feedback loop) b. unregulated receptor expression -> increased sensitivity to ligand c. stimulate normal cells to supply GF's d. constitutively activate signalling pathways downstream of receptors -> no need

Question 29

How do normal cells evade growth supressors

Answer 29

use antigrowth signals to maintain quiescence & homeostasis - these signals block proliferation by forcing cells: - to enter quiescent G0 state -> cell cycle arrest - permanently lose their proliferative potential -> interim post-mitotic state, senescence, apoptosis cells can re-emerge from G0 state on some future occasion when extracellular signals permit

Question 30

How do cancer cells evade growth supressors?

Answer 30

circumvent antigrowth programs (evade TGF-beta anti proliferative signalling) - many antigrowth programs depend on tsg (tp53, PTEN &RB) - complete loss of TSG - accumulation of mutations that render genes inactive

Question 31

What can cancer cells become in growth signals?

Answer 31

self sufficient in growth signals also become insensitive to antigrowth signals

Question 32

What are the different types of genetic mutations in cancer?

Answer 32

missense frameshift nonsense chromosome rearrangements