Cancer Cell Biology
What Causes Cancer
Environmental carcinogens cause mutation
DNA damage and mutations are also caused by endogenous factors produced by normal
cellular metabolism
DNA damage can lead to mutations
o UV light commonly induces cyclobutene pyrimidine dimers (CPD)
o Cytosine residues with CPD deaminate into uracil
o This induces a C > T mutation
DNA Damage Repair
5 main pathways for repair
o Direct repair
o Base excision repair
o Nucleotide excision repair
o Mismatch repair
o Double stranded break repair
Inherited defects in these pathways increase the risk of cancer
Nucleotide Excision Repair Mutations
Mutations cause Xeroderma pigmentosum
Autosomal recessive disease with very high risk of skin cancer
NER is the only pathway to remove UV-induced pyrimidine dimers in humans
16 NER proteins in humans
Types of Mutations
Germline mutations
o Present in eggs or sperm
o Are heritable
o Causes hereditary cancer
, Somatic mutations
o Occur in non-germline tissues
o Are non-heritable
o Later onset
Gene Mutations
Oncogene
o A gene that played a normal role in the cell that has been altered by mutation and
now may contribute to growth of tumour
Tumour suppressor genes
o A protective gene that normally limits the growth of tumour
Gatekeepers
o Genes that directly regulate tumour growth by inhibiting tumour growth or
preventing death
Caretakers
o Inactivation leads to genomic instability and increased risk of mutation in all genes
Knudson’s 2-hit Hypothesis
That tumour suppressor genes require both alleles to be inactivated to cause a phenotypic
change
Cancer Hallmarks
Evading growth suppression
Avoiding immune destruction
Enabling replicative immortality
Tumour promoting inflammation
Activating invasion and metastasis
Inducing or accessing vasculature
Genome instability and mutation
Resisting cell death
Deregulating cellular metabolism
Sustaining proliferative signalling
What Causes Cancer
Environmental carcinogens cause mutation
DNA damage and mutations are also caused by endogenous factors produced by normal
cellular metabolism
DNA damage can lead to mutations
o UV light commonly induces cyclobutene pyrimidine dimers (CPD)
o Cytosine residues with CPD deaminate into uracil
o This induces a C > T mutation
DNA Damage Repair
5 main pathways for repair
o Direct repair
o Base excision repair
o Nucleotide excision repair
o Mismatch repair
o Double stranded break repair
Inherited defects in these pathways increase the risk of cancer
Nucleotide Excision Repair Mutations
Mutations cause Xeroderma pigmentosum
Autosomal recessive disease with very high risk of skin cancer
NER is the only pathway to remove UV-induced pyrimidine dimers in humans
16 NER proteins in humans
Types of Mutations
Germline mutations
o Present in eggs or sperm
o Are heritable
o Causes hereditary cancer
, Somatic mutations
o Occur in non-germline tissues
o Are non-heritable
o Later onset
Gene Mutations
Oncogene
o A gene that played a normal role in the cell that has been altered by mutation and
now may contribute to growth of tumour
Tumour suppressor genes
o A protective gene that normally limits the growth of tumour
Gatekeepers
o Genes that directly regulate tumour growth by inhibiting tumour growth or
preventing death
Caretakers
o Inactivation leads to genomic instability and increased risk of mutation in all genes
Knudson’s 2-hit Hypothesis
That tumour suppressor genes require both alleles to be inactivated to cause a phenotypic
change
Cancer Hallmarks
Evading growth suppression
Avoiding immune destruction
Enabling replicative immortality
Tumour promoting inflammation
Activating invasion and metastasis
Inducing or accessing vasculature
Genome instability and mutation
Resisting cell death
Deregulating cellular metabolism
Sustaining proliferative signalling
