Cancer in Families and Individuals Flashcards
What causes dysregulated growth of cancer?
pro-growth signalling and insensitive to anti-growth signalling
sustained angiogenesis
What causes disorder death of cancer?
evasion of apoptosis and limitless replication
What causes disordered behaviour of cancer?
promotion of inflammation, dysregulation of energy metabolism, evasion of immune system, invasion + metastasis
define polyclonal
many distinct cells
How are driver mutation used clinically?
understand how disease develops
increase diagnosis accuracy
targeted therapy
monitor therapy response
What is the function of tumour suppressors?
regulate cell division by
- acting as a G1-S checkpoint in cell cycle
- mediate mitosis
- tell damaged cells to apoptose or DNA repair pathway
What is the function of proto-oncogenes
promote growth and proliferation using growth factors, TFs and tyrosine kinase
What is the Knudsons 2-hit hypothesis? What happens at each hit?
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
define somatic mutation
mutation in somatic tissue e.g causes cancer
define germline mutation
mutation in germ cells (gamete cell line) so may cause inheritable disease
Difference between driver and passenger mutations
driver mutation confers a selective growth advantage whilst passenger mutations don’t
What is loss of heterogeneity in tumour suppressor cells?
large portion of 2nd TS gene chromosome is deleted so large portion of SNPs erased as only 1 chromosome
What gene predisposes people to breast and ovarian cancer? What does BRCA cause
BRCA 1/2
impaired DNA repair
How are inherited cancers managed?
family history
genetic screening
genetic counselling
surveillance, surgery, chemo prevention
What is genome wide association studies?
large patient cohort study
includes SNP fishing (seeing is SNP frequency related to disease) to identify genes of interest
What is chronic myeloid leukaemia?
a clonal myeloproliferative disorder resulting in over production of mature granulocytes
What are the 3 phases of CML?
1) chronic = benign
2) accelerated = ominous
3) blast crisis = fatal
What is the Philadelphia translocation? What does it do?
translocation between chromosome 9 and 22
creates BCR-ABL1 fusion protein which causes cancer behaviour
What is imatinib used for?
targeted therapy to block BCR-ABL1 binding site for ATP
What is acute premyelocytic leukaemia?
translocation between Chr 15 and 17 resulting in accumulation of promyelocytes
How is CML monitored?
q-RT-PCR
Why is the residual CML quantified?
initial response defines long-term response and guide clinical management e.g. change of therapy if RT-qPCR negativity lost
What is RARalpha?
a nuclear bound retinoid acid and regulator of transcription
What does PML-RARalpha do?
bind to DNA too strongly and blocks transcription and granulocyte differentiation
