Cancer Genetics and Genomics Flashcards
(25 cards)
Distinguish between genetics and genomics
Genetics: individual genes
Genomics: considering all genes and their interactions
Distinguish between variant, mutation and polymorphism
Variant: any change from reference DNA sequence
Mutation: variant causing disease
Polymorphism: variant not causing disease
Distinguish between somatic, driver and passenger mutations
Somatic mutation (variant): any change from pt’s germline DNA
Driver mutation: somatic mutation contributing to cancer development
Passenger mutation: somatic mutation not contributing to cancer development
What is a mutator phenotype?
Occurs in cancer when DNA repair mechanisms are lost, thereby increasing the rate of mutation
How many driver and passenger mutations are there estimated to be per cancer?
5-10 driver
1000s-100,000s passenger
List the 10 hallmark functional characteristics of cancer cells
Sustained proliferative signalling Evading growth suppression Resisting cell death Inducing angiogenesis Replicative immortality Invasion and metastasis Deregulated cellular energetics Avoiding immune destruction Genome instability and mutation Tumour-promoting inflammation
What healthy tissues are also damaged in standard chemotherapy?
BM
GIT
Skin
What are the key genes involved in the MAPK signalling pathway?
EGFR
HER2
KRAS
BRAF
What is the hallmark of alterations to the MAPK signalling pathway?
Sustained proliferative signalling
What is HER2?
Growth factor receptor which signals via the MAPK and other pathways
What % of breast cancers have a HER2 gene amplification? How and why is this tested for?
~20%
In situ hybridisation (ISH) testing for HER2 amplification performed on all breast cancers to guide use of targeted therapies
What is trastuzumab?
Monoclonal Ab which interfers with HER2 function and/or induces immune destruction of cells bearing HER2
What is BRAF?
An important signalling protein in the MAPK pathway
In what cancer is the BRAF V600E mutation commonly seen?
Melanomas (~50%)
What is vemurafinib?
Small-molecule inhibitor of V600E mutant BRAF
When is BRAF V600E mutation testing commonly performed?
For metastatic melanoma
In what cancer are activating EGFR mutations seen?
Non-small cell lung cancers (~15% of all NSCLC)
What are gefitinib and erlotinib?
Small-molecule EGFR inhibitors
When is EGFR mutation testing performed?
Standard of care for NSCLC
What is cetuximab and when is it used?
Monoclonal Ab that inhibits EGFR
EGFR is expressed in most colorectal cancers but is unmutated; despite this, cetuximab is an effective treatment
When is cetuximab not effective in treating colorectal cancer? Why? What are the clinical implications?
In pts whose tumours have activating KRAS mutations
RAS is downstream in the MAPK pathway; if the pathway is activated at this level, treatment targeted to the receptor will have no effect
KRAS mutation testing is required before commencing cetuximab
What is imatinib? When is it indicated?
An inhibitor of multiple TKs
In case of the BCR-ABL fusion gene in CML and some ALLs, and c-Kit mutation in GI stromal tumours
What is sorafenib? When is indicated?
Inhibits RAF and VEGFR
Used in HCC and RCC
What is the transcriptome?
RNA expression analysis
