Chapter 20: Cancer Genetics and Genomics

Cancer

abnormal growth that invades and spreads

What is the relationship between genes and cancer?

Genetic changes can lead to cancer if they alter the way your cells grow and spread

3 cellular pathways affected by cancer-causing gene mutations

1. Cell fate: differentiation

2. Cell survival: oxygen availability & preventing apoptosis

3. Genome maintenance: ability to survive in presence of reactive oxygens species

Distinguish between a benign and a malignant tumor.

Benign: does not spread or invade surrounding tissue

Malignant or cancerous: invade other tissues

Why is metastasis dangerous?

When tumor detaches and spread to far regions of the body via blood or lymph which makes cancer difficult to detect and treat

Define carcinogens

substances that cause cancer

What are the 3 categories of cancer critical genes

1. Oncogenes (100+)

2. Tumor suppressor genes (30+)

3. DNA repair genes

What are oncogenes?

-Mutated versions of proto-oncogenes (normal genes that control normal growth)

-Cause cancer if inappropriately activated

-Dominant gain-of-function (only one dominant mutation is needed to cause a cell to become cancerous)

What are tumor suppressor genes?

-Control cell cycle checkpoints & apoptosis

-Cause cancer when deleted or inactivated

-Recessive loss-of-function mutations (knock out 2 copies of TSG for cancer to result)

What are DNA repair genes?

-Allow other mutations to persist

-Inherited in a single-gene function > cause diverse and widespread tumors

What happens when there is a mutation in the gene that controls the cell cycle

There will be inappropriate mitosis and failure to pause and repair DNA will cause mutations to persist

Explain how the loss of control of telomere length may contribute to cancer

Telomerase keeps telomeres long in gametes and stem cells > if telomerase is left on, telomerase extend and there is no brake on rapid cell division

Describe two abnormalities of chromosomes in cancer cells.

Aneuploidy is when there is a missing or extra chromosome

Translocation can increase expression of a gene

What is the difference between Inherited (germline) and Sporadic (somatic) mutations

Germline mutations when gametes (10% of cases) are affected

-passed on to offspring (mutation present in all cells of the individual)

-cancer develops when 2nd somatic mutation occurs

Somatic mutations occur sporadically in non-sex cells (90% of cases)

List the characteristics of cancer cells

-Contain heritable mutations (passed to daughter cells)

-Dedifferentiated (less specialized than normal cell types)

-Unusual cell growth (no contact inhibition)

-Invasive (squeeze into any space)

-Metastatic (able to move to new locations)

-Induce angiogenesis (formation of new capillaries)

-Secrete hormones that encourage their own growth

-Aneuploid (missing or extra chromosomes)

Explain how cancers form from shifting the balance of cell types in a tissue

Cancers result from the loss of balance at the tissue level that favors cells that can divide continually or frequently

Mutation shifts balance to create more stem and progenitor cells > tumor formation

List and the 3 strikes of cancer

1. Breakthrough

2. Expansion

3. Invasion

Describe the strike of cancer: Breakthrough

1st driver mutation in a gatekeeper (oncogene on or tumor suppressor gene off) enables a normal cell to divide faster clones accumulate

Describe the strike of cancer: Expansion

2nd driver mutation boosts division rate cancer cells divide more frequently & survive in harsh environments

Describe the strike of cancer: Invasion

further mutations in multiple pathways cancer grows and spreads

How do environmental factors contribute to cancer

by mutating or altering the expression of genes that control the cell, apoptosis, and DNA repair

True or false: Both environmental and genetic factors contribute to cancer risk

True

Is melanoma only caused by environmental factors (sun exposure)? Explain why or why not

No, melanoma can also be caused by the variant of melanocortin-1 receptor (MC1R) gene