Genetics Chapter 23

Exam 3

What are proto-oncogenes?

Promote cell division

What proteins promote cell division?

RAS, C-myc, Src, C-fos

What are tumor suppressors?

Inhibit cell division

What proteins inhibit cell division?

p53, pRb, BRCAI

What are mutations associated with cancer?

Cell cycle genes, DNA repair genes, Checkpoint genes, Angiogenic factors

What does abnormal proliferation of cancer cells produce?

A tumor that crowds our normal cells

• characteristic of original breast tumor

What is a benign tumor?

The tumor remains localized

What is a malignant tumor?

Tumor cells invade other tissues

What is metastasis

the tumor cells induce secondary tumors

What are examples of genetic evidence for cancer?

Carcinogens, chromosomal abnormalities, inheritance

What is Knudson’s multistep model of cancer?

Requires several mutations

What is the clonal evolution of tumors?

Tumor cells acquire more mutations; allows them to become increasingly more aggressive in their proliferate properties

What did Alfred Knudson propose?

Retinoblastoma results from two separate genetic defects, both of which are necessary for cancer to develop

What occurs through clonal evolution?

Tumor cells acquire multiple mutations that allow them to become increasingly aggressive and proliferative

Is cancer a genetic disease that is mostly inherited?

No; cancer is a genetic disease but most are NOT inherited

What are factors contributing to cancer?

Tobacco use, obesity, alcohol, UV radiation

Are oncogenes dominant or recessive? How many copies are required?

Oncogenes mutations are dominant. One copy is needed for the mutation

Are tumor suppressors dominant or recessive? How many copies are required?

recessive mutations; cell needs both copies to be insulated

What are oncogenes?

Mutated, dominant-acting, stimulatory genes that cause cancer

What are proto-oncogenes?

Responsible for basic cellular functions in normal cells; when mutated, they become oncogenes

What are tumor-suppressor genes?

Mutated recessive-acting inhibitory genes that are inactive. If a copy of tumor-suppressor gene is deleted, a loss of heterozygosity occurs

What does loss of heterozygosity often lead to?

Often leads to cancer in a person heterozygous for a tumor-suppressor gene

What gene is in control of the cell cycle?

Cyclin-dependent kinases (CDKs), cyclins

What gene is in control of G1-to-S transition?

Retinoblastoma protein (RB)

What gene is in control of G2-to-M transition?

Mitosis-promoting factor (MPF)

What is the purpose of the spindle assembly checkpoint?

Leads to arrest of cell cycle

How is CDK regulated?

tightly regulated at the level of phosphorylation

How are cyclins regulated?

Regulated at mRNA and protein levels

What happens when CDK binds to cyclin?

It becomes active; CDK by itself is inactive

What is Rb

tumor suppressor

How does the RB protein help control progression through G₁/S checkpoint?

It binds to the transcription factor e2F; this promotes specific genes

What is progression through the G₂/M checkpoint regulated by?

Cyclin B

What is a signal-transduction pathway?

Signals trigger a cascade of intracellular reactions, producing a specific response; related to the Ras protein

What is Ras-GTP?

Active

What is Ras-GDP?

Inactive

What does the Ras signal-transduction pathway do?

Conducts signals from growth factors and hormones to the nucleus and stimulates the cell cycle

What happens if Ras-GTP is always on?

Cell proliferation

What happens if dimerization is always on?

Cell proliferation; regardless if Ras is bound to GDP or GTP

What are mutations in Genes that control the cycle of cell division?

DNA-repair genes, genes that regulate telomerase, genes that promote vascularization and the spread of tumors, MicroRNAs and cancer, and cancer genome projects

What is the purpose of the International Cancer Genome Consortium?

Coordinates efforts to determine the genome sequences of tumors

What is the purpose of the Cancer Genome Atlas (TCGA)?

A comprehensive genomic analysis of over 100 different types of cancer cells

What alterations are seen in many cancers?

Alterations to DNA methylation or chromatin structure; hypermethylation or hypomethylation

What is important to know about hypermethylation/hypomethylation

Reversible and not a mutation

What is colorectal cancer an example of?

Sequential Mutation

What did colorectal cancer lead to?

Led to tumor progression model

What is a general feature of cancer cells?

Chromosomal instability

Which chromosomal instabilities are general features of cancer cells?

• Deletions, inversions, and translocations

• Aneuploidy

What is an example of chromosomal instability that leads to cancer?

A reciprocal translocation between chromosomes 9 and 22 causes chronic myelogenous leukemia

What can happen between chromosomes 8 and 14?

A reciprocal translocation between chromosomes 8 and 14 causes Burkitt lymphoma

How can extensive aneuploidy occur?

Loss of checkpoint control

How do retroviruses cause cancer?

Mutating and rearranging proto-oncogenes, and inserting strong promoters near proto-oncogenes

What are examples of retroviruses?

Human papillomavirus and cervical cancer