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

#genomics