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.