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Lecture 21

HMB265H1 Lecture Notes - Lecture 21: Spindle Checkpoint, Spindle Apparatus, Dna Microarray


Department
Human Biology
Course Code
HMB265H1
Professor
Maria Papaconstantinou
Lecture
21

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Genetics of Cancer
Cancer cell characteristics
o Mutations in genes that regulate cell division and growth
Occur in somatic cells
Mutations accumulate
Inherited ones predispose someone to cancer
e.g. retinoblastoma
o Autocrine stimulation
o Loss of contact inhibition
o Loss of gap junctions
o Defects in DNA repair machinery
o Anigogenesis, metastasis, evasion of of immune surveillance
Oncogenes - cause proliferation and are members of signal transduction
pathways
o How to identify
tumor-causing viruses
tumor DNA
Microarrays
Genome wide functional screens
Transform mouse cells to ones with human tumor DNA
o Examples - constitutive activation
RAS - can proliferate with out ligand; over-active receptor
Bcr/c-ABl - fusion causes overactive receptor
Her2 - high levels of receptor present
Tumor suppressor genes - stops cell cycle, cell proliferation, promotes
apoptosis and DNA repair
o E.g retinaoblastoma
Loss of heterozygosity
o Checkpoints - can delay to allow time to repair DNA
G1-S
p53
G2-M
Spindle checkpoint
o Chemotherapy - kills proliferating cells by disruoting
DNA replication and formation of mitotic spindle
Personalized Medicine
o Target oncogenes
e.g. Gleevec targets bcr/c-abl
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