The Genetics of Cancer

Human and Cancer

Life and adaptation

cell division

Cancer in the media

cancer is a disease of the cell cycle

Synth. Of RNA & proteins

Cont. Of RNA

Chromosomes are attached to the spindle

G1 checkpoint

G1

S

M

M checkpoint

G2 checkpoint

G2

Controlsystem

DNA damage or broken

In complete DNA replication

G1

G1 checkpoint

G1

G0

If a cell receives a go-ahead signal at the G1 checkpoint, the cell continues on in the cell cycle.

If a cell does not receive a go-ahead signal at the G1 checkpoint, the cell exits the cell cycle and goes into G0, a nondividing state.

Unlimited number of cell divisions.Growth without external signals.Failure to respond to 'stop' signalsAvoidance of cell death.The ability to leave the original tumor location and form a new tumor, or metastasis.

Cancer terminology

Classification by tissue type:• carcinoma

epithelial cell90% of all tumoursderived from ectoderm (mostly) or endoderm (some)

• sarcomaconnective tissue2% of all tumoursderived from mesoderm

• leukaemiacirculatory or lymphatic8% of all tumoursderived from mesoderm

• Myeloidblood cell

• Lymphoidlymphocytes or macrophages

• Central nervous system cancers of the brain

Main Features of Benign and Malignant Tumors

Cancer Spreads Step-by-Step

A Common Type of Colorectal Cancer May Develop by These Steps

Types of genes which may mutate to cause cancer:

• Tumor suppressor genes– Stop cell growth and division; prevent cancer

formation– May prevent expression of oncogenes– Retinoblastoma: only one functional copy of a

tumor suppressor gene on chromosome 13– BRCA1 and BRCA2– p53: codes for a regulatory protein that turns off

cell division when the cell is stressed or damaged

Types of cancer genes

Types of proteinsTypes of proteinsMutated functionMutated functionNormal functionNormal functionType of geneType of gene

Enzymes for mismatch or excision repair

Fail to repair DNA mutations

Repair DNA mutations

DNA repair gene mutation

Checkpoint molecules

Fails to suppress division

Suppresses cell division

Tumor suppressor gene

Growth factorsPromotes division - abnormal time or cell type

Promotes divisionOncogene

Tumour suppressor genes

• The gene’s normal function is to regulate cell division. Both alleles need to be mutated or removed in order to lose the gene activity.

• The first mutation may be inherited or somatic.• The second mutation will often be a gross event

leading to loss of heterozygosity in the surrounding area.

Oncogenes

• Cellular oncogene c-onc• Viral oncogene v-onc• Proto-oncogene, activated by mutation

to c-onc

Proto-oncogene activation

Other Factors Also May Lead to Cancer

• Inherited susceptibility to cancer– ~5% of cancers

• Viruses– Viral DNA may be inserted into a host cell’s DNA • May switch on a proto-oncogene• May carry oncogenes

Other Factors Also May Lead to Cancer

• Chemical carcinogens– Carcinogens: cancer-causing substances that can

lead to a mutation in DNA• Hydrocarbons in cigarette smoke• Aflatoxin: fungal product

• Radiation– UV from the sun and tanning lamps– X-rays: medical and dental– Radon, cosmic rays, and gamma radiation

Some Industrial Chemicals Linked to Cancer

In the U.S., More than 1 Million People Are Diagnosed with Cancer Each Year

Biopsy Is the Only Sure Way to Diagnose Cancer

• Biopsy– Removal and microscopic examination of tissue

Light Microscope Image Shows Cancerous Cells in Breast Tissue

Cancer Treatment and Prevention

• When a person is diagnosed with cancer, a variety of weapons are available to combat it

Chemotherapy drugs

Radiation therapy

Surgery

Chemotherapy and Radiation Kill Cancer Cells

• Chemotherapy– Drugs used to kill cancer cells; disrupt some aspect

of cell division– Toxic to healthy cells; hair, bone marrow,

lymphocytes, and epithelial cells of intestinal lining – Side effects include hair loss, nausea, vomiting, and

reduced immune responses– Genetic approach to chemo in the future

Chemotherapy and Radiation Kill Cancer Cells

• Radiation therapy– Used when cancer is small or has not

spread– Radioisotopes used, e.g., Ra-226 and

Co-60

• Chemotherapy and radiation destroy healthy cells

• More precise treatments– Monoclonal antibody treatment– Interferon treatment; limited at

present

Good Lifestyle Choices Can Limit Cancer Risk

• Avoid tobacco completely

• Maintain a desirable weight; eat a low-fat diet with plenty of fruits and vegetables

• Drink alcohol in moderation

• Make sure your living and work environment is safe from carcinogens

• Protect your skin from the sun’s UV rays

This Cancer Cell Is Surrounded by White Blood Cells

Cancer Causes and Contributing Factors

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