Cancer in Families and Individuals

Question 1

What causes dysregulated growth of cancer?

Answer 1

pro-growth signalling and insensitive to anti-growth signalling
sustained angiogenesis

Question 2

What causes disorder death of cancer?

Answer 2

evasion of apoptosis and limitless replication

Question 3

What causes disordered behaviour of cancer?

Answer 3

promotion of inflammation, dysregulation of energy metabolism, evasion of immune system, invasion + metastasis

Question 4

define polyclonal

Answer 4

many distinct cells

Question 5

How are driver mutation used clinically?

Answer 5

understand how disease develops
increase diagnosis accuracy
targeted therapy
monitor therapy response

Question 6

What is the function of tumour suppressors?

Answer 6

regulate cell division by

• acting as a G1-S checkpoint in cell cycle
• mediate mitosis
• tell damaged cells to apoptose or DNA repair pathway

Question 7

What is the function of proto-oncogenes

Answer 7

promote growth and proliferation using growth factors, TFs and tyrosine kinase

Question 8

What is the Knudsons 2-hit hypothesis? What happens at each hit?

Answer 8

tumour suppressor gene require 2 damages alleles
hit 1 - reduces transcription and protein level but no phenotypic effect POINT MUTATION
hit 2 - inactive second allele causes total loss of transcription DELETION MUTATION

Question 9

define somatic mutation

Answer 9

mutation in somatic tissue e.g causes cancer

Question 10

define germline mutation

Answer 10

mutation in germ cells (gamete cell line) so may cause inheritable disease

Question 11

Difference between driver and passenger mutations

Answer 11

driver mutation confers a selective growth advantage whilst passenger mutations don’t

Question 12

What is loss of heterogeneity in tumour suppressor cells?

Answer 12

large portion of 2nd TS gene chromosome is deleted so large portion of SNPs erased as only 1 chromosome

Question 13

What gene predisposes people to breast and ovarian cancer? What does BRCA cause

Answer 13

BRCA 1/2

impaired DNA repair

Question 14

How are inherited cancers managed?

Answer 14

family history
genetic screening
genetic counselling
surveillance, surgery, chemo prevention

Question 15

What is genome wide association studies?

Answer 15

large patient cohort study

includes SNP fishing (seeing is SNP frequency related to disease) to identify genes of interest

Question 16

What is chronic myeloid leukaemia?

Answer 16

a clonal myeloproliferative disorder resulting in over production of mature granulocytes

Question 17

What are the 3 phases of CML?

Answer 17

1) chronic = benign
2) accelerated = ominous
3) blast crisis = fatal

Question 18

What is the Philadelphia translocation? What does it do?

Answer 18

translocation between chromosome 9 and 22

creates BCR-ABL1 fusion protein which causes cancer behaviour

Question 19

What is imatinib used for?

Answer 19

targeted therapy to block BCR-ABL1 binding site for ATP

Question 20

What is acute premyelocytic leukaemia?

Answer 20

translocation between Chr 15 and 17 resulting in accumulation of promyelocytes

Question 21

How is CML monitored?

Answer 21

q-RT-PCR

Question 22

Why is the residual CML quantified?

Answer 22

initial response defines long-term response and guide clinical management e.g. change of therapy if RT-qPCR negativity lost

Question 23

What is RARalpha?

Answer 23

a nuclear bound retinoid acid and regulator of transcription

Question 24

What does PML-RARalpha do?

Answer 24

bind to DNA too strongly and blocks transcription and granulocyte differentiation

Question 25

What does ATRA therapy do? Why is it good/bad?

Answer 25

dissociate co-repressors and allows transcription and differentiation
doesn’t kill cells but requires continuous therapy as residual stem cells remain

Question 26

What are cytogenetic changes?

Answer 26

visible changes in chromosome structure