Genes and Cancer

1
Genes and Cancer
2
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)

3
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)

4
Metastasis
Trialx.com
Nature.com
5
First mutation
Second mutation
6
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

7
Model of cell activation
Bio.miami.com
8
Mutations in regulatory genes implicated in cancer

• RB1- tumor suppressor , controls progression from
  G1 to S
• Ras proto-oncogenes mutants are always switched
  on

9
Nature.com
Ras proteins mutated at Aa 12 or 61
Wormbook.org
10
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

11
Multistep model for colon cancer
APC K-ras DCC
p53
p53 implicated in about half of all cancers
12
Li- Fraumeni syndrome a mutation in p53
13
Inheritance of von Hippel-Lindau syndrome
14
Chromosomal translocations- hereditary cancer
Found in several leukemias And lymphomas Burkit
ts lymphoma
www.nobelprize.org
15
What causes cancer?

• Minority of cancers are inherited
• Environmental factors
• Carcinogens
• Viruses
• Diet
• Etc.

16
How do we study causes of cancer?

• Population studies
• Case-control studies
• Prospective studies

17
Treatment strategiesExample breast cancer

• strategy

• example

• Removal
• Match phenotype to treatment
• Use genotype to select drug

• Surgery, radiation, chemotherapy
• Target estrogen receptor if present
• Depends on presence of cancer-specific gene
• Microarrays make rapid diagnosis possible

18
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

19

• 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.