genes and cancer
Post on 22-Feb-2016
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Genes and Cancer
What is cancer?
• Uncontrolled cell growth• Ability to spread to other parts of the body• Generally a disease of aging• Tumors are named according to the tissue
from which they form– Benign (do not spread)– Malignant (can metastasize)
Is cancer genetic?
• “Predisposition” can be inherited• Most mutagens are carcinogens• Cancer genes can be spread by viruses• Some cancers are know to be cause by
chromosome abnormalities• Most cancers are sporadic (not inherited)• Cancers are caused by damage to DNA
(mutation)
Trialx.com
Nature.com
Metastasis
First mutation Secondmutation
The cell cycle and regulation• Cell division usually closely
regulated• Checkpoints control
transition through stages– Tumor suppressor genes– Proto-oncogenes
• Triggered by signal transduction
• Loss of control leads to tumor formation
Bio.miami.com
Model of cell activation
Mutations in regulatory genes implicated in cancer
• RB1- tumor suppressor , controls progression from G1 to S
• Ras proto-oncogenes: mutants are always switched on
Nature.com
Wormbook.org
Ras proteins mutated atAa 12 or 61
Genomic stability and hereditary cancer
• BRCA 1 and BRCA 2 (breast, ovary prostate)• more information• p53: whether cell is repaired or undergoes apoptosis• Abl- proto-oncogene, white blood cells• Some genes are widely distribute; some restricted to
specific tissues
Multistep model for colon cancer
APC K-ras DCC
p53
p53 implicated in about half of all cancers
Li- Fraumeni syndrome: a mutation in p53
Inheritance of von Hippel-Lindau syndrome
www.nobelprize.org
Chromosomal translocations- hereditary cancer
Found in several leukemiasAnd lymphomas
Burkitt’s lymphoma
What causes cancer?
• Minority of cancers are inherited• Environmental factors
– Carcinogens– Viruses– Diet– Etc.
How do we study causes of cancer?
• Population studies• Case-control studies• Prospective studies
Treatment strategiesExample: breast cancer
strategy• Removal
• Match phenotype to treatment
• Use genotype to select drug
example• Surgery, radiation,
chemotherapy• Target estrogen receptor if
present• Depends on presence of
cancer-specific gene• Microarrays make rapid
diagnosis possible
Summary
• Cancer is caused by genetic mutation, but is usually not inherited
• Tumor cells divide uncontrollably• Tumors can arise in a variety of cells• Proto-oncogenes, tumor suppressor genes,
and DNA repair genes are implicated in cancer• Cancers can arise from two or more mutations
• Population studies in conjunction with biochemical and genetic studies can help explain causes of cancer
• Molecular and genomic studies are used to develop treatments that are specific to the type of tumor.
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