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University of Toronto St. George
Molecular Genetics and Microbiology
Johanna Rommens

April 4, 2013 CANCER GENETICS - inherited syndromes with defect s in DNA repair Longer the exposure, more opportunity for evn to affect the genome – syndromes where deficiencies in DNA repair are seen – concern genes with development of cancer – can aggregate the concern that the genome is changing – Development of cancer involves changes in genes Acquired changes in somatic cells – older age Damage to DNA, errors in DNA replication Damage invoke repair mechanisms – humans have extensive repair processes that work – base excision repair, doublestranded break repair, etc. – encompassing homologous recombination Replication error repair = mistmatch repair is important – envisage the genome is sensitive to changes – nucleotide excision repair – this may invoke changes in genome – nucleotide excision repair corrects covalent modifications of DNA Thymidine cross-links – lead to cancers in skin – where exposed area would be Areas of exposure where the damge is seen – Nuicleotide excision repair – learned from inherited diseases that show defects in the process – ex xeroderma pigmentosum – Mismatch repair – Double stranded break repair – serious for cell – Translocations – Philadelphia chromosome – CANCER is disease of older age – need time for the mutations to occur, for this clonal expansion of mutations to occur Vogelstein – SMAD, Cancer is multi-step evolution Order of insults may not be specific or not all necessary – partly because multiple routes to the development of cancer- Pathway of dev
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