CANCER GENETICS
HUMAN GENOME
GENES 1.5%
Proteins
non-coding RNA
RELATED SEQUENCES 40%
Introns
Transcriptional regulatory regions including 5’ and 3’ UTRs
Pseudogenes and segmental duplication
REPETITIVE DNA 45%
Interspersed regions
Mini and microsatellites
Telomeres
Centromeres
SOMATIC MUTATIONS
Inactivate a “tumour suppressor gene”
Activate an “oncogene”
Create a new “fusion gene”
TUMOUR SUPPRESSOR GENES
Important for controlling rate of cell growth
Typically diploid
Sporadic cancer occurs with bi-allelic loss/mutation
Heterozygous constitutional mutations result in increased cancer risk
ONCOGENES Accelerate cell division
Cancer arises when stuck in “on” mode - a gain of function mutation
DNA DAMAGE-RESPONSE/REPAIR GENES Constantly repairing DNA
Cancer arises due to accumulation of mutations across the genome
BRCA1, BRCA2
Most cancer susceptibility genes are Dominant with Incomplete penetrance.
DIAGNOSTIC TEST: full screen of a gene, taken in an individual with a condition
PREDICTIVE TEST: targeted test for a specific mutation identified in another family member, normally undertaken in an unaffected individual
SOMATIC CANCER GENETICS
Mutations within clones of cells that drive cancer development and spread, used for prognosis, therapy choices and research.
CONSTITUTIONAL CANCER GENETICS
Mutations in cancer predisposition genes, often inherited and present in every cell, younger onset cancer, risk of multiple primaries, frequently associated with family history of same cancer or pattern of cancers