Genetics Chapter 18

Checking DNA pieces in the blood plasma for oncogene or tumor suppressor mutations is termed a ____________

"liquid biopsy."

About ____ percent of all of our genes are involved in the cell cycle or DNA repair and can be implicated in some way in cancer.

1

Inherited Cancer

10 percent of cases result from inheriting a cancer susceptibility allele from a parent. The inherited allele is a germline mutation, meaning that it is present in every cell of the individual, including the gametes. Cancer develops when a second mutation occurs in the other allele in a somatic cell in the affected body part.

Distinguish between a benign and a cancerous tumor.

Benign grows in place and does not spread and cancerous if it infiltrates nearby tissue.

REFER TO FIGURE 18.6 Stem cells, cancer stem cells, early progenitor cells, and abnormal daughter cells all have the ___________ marker, but the differentiated cells did not

CD133+

Discuss the role of chromosomes in causing cancer

Chromosome abnormalities can cause mutations in oncogenes and tumor suppressor genes.

Explain how testing for mutations and for gene expression patterns can help a physician to select a treatment for a patient.

Gene expression profiling can specifically describe the type of cell that turns cancerous, which informs treatment choices.

Which type of cancers are rare, but they have high penetrance and tend to strike earlier in life?

Germline (inherited)

Discuss how chimeric antigen receptor technology treats a cancer

It creates DNA instructions for a hybrid surface protein on T cells that the body does not normally synthesize. The protein, called a chimeric antigen receptor, or CAR, is part T cell receptor and part antibody. The receptor part is engineered to guide the T cell to a specific target, such as cancer cells. The antibody part then binds the target, alerting the immune system to respond and kill the cancer cells.

Explain how a sporadic cancer differs from a Mendelian disease in terms of predicting risk of occurrence in the relatives of a patient

Mendelian diseases are inherited through the germline. Relatives can be tested for genes that affects the disease. Sporadic cancer cells arises from 2 mutations in the somatic cells. This would not increase the risk for the relatives. The cancer can come from one dominant gene or 2 recessive mutations.

What is the relationship between genes and cancer?

Most substances known to be carcinogens (causing cancer) are also mutagens (damaging DNA) Most mutations that cause cancer are in oncogenes or tumor suppressor genes.

What are the characteristics of cancer cells?

Oilier, less adherent, Loss of cell cycle control, Heritable, Transplantable, Dedifferentiated, Lack contact inhibition, Induce local blood vessel formation (angiogenesis), Invasive, Increased mutation rate, Can spread (metastasize)

Mutation in tumor suppressor genes can cause what conditions?

Retinoblastoma (eye tumor) Stomach Cancer (from E-cadherin deletion) Breast cancer (only 5% from familial),

A cancer cell may descend from a ________ _______ that yields slightly differentiated daughter cells that retain the capacity to self-renew, or a cancer cell may arise from a ___________ __________ that loses some of its features and can divide. Certain stem cells, called cancer stem cells, veer from normal development and produce both cancer cells and abnormal specialized cells. Cancer stem cells are found in cancers of the brain, blood, and epithelium (particularly in the breast, colon, and prostate).

Stem Cell, specialized cell

Mutation in the gene that encodes telomerase, called _______, causes some cancers.

TERT

Explain how altering the balance between stem and progenitor cells and differentiated cells, or excess tissue repair, can cause cancer

The cancerous growth takes place due to onset of un-controlled cellular division which results in formation of a tumor. This un-controlled cell-division takes place due to genetic disturbances

Sporadic cancers

The majority of cancers are sporadic, and caused by somatic mutations, which affect only non-sex cells. A sporadic cancer may result from a single dominant mutation or from two recessive mutations in copies of the same gene. The cell loses control of its cell cycle, and accelerated division of its daughter cells forms the tumor.

Contrast traditional approaches to diagnosing and treating cancer to newer methods

Traditional Dx=symptoms> test such as scans>biopsies Traditional Tx= Surgery, Chemo, Radiation Newer Methods dx= Gene expression profiling Newer Methods Tx= surgery, targeted tx based on genetic information: tyrosine kinase inhibitor Gleevec, chimeric antigen receptor technology

T/F A Glimpse of History describes the fusion protein that led to the development of Gleevec, one of the first cancer drugs targeted to cell with specific mutations.

True

T/F Cancer can result when a tumor suppressor gene is deleted or if the promoter region binds too many methyl (CH3) groups, which blocks transcription.

True

True or False: Proto-oncogenes can also become oncogenes by being physically next to highly transcribed genes. Three examples of genes that can activate proto-oncogenes are a viral gene, a gene encoding a hormone, and parts of antibody genes.

True

True/False: Cancer cells divide more frequently or more times than the cells from which they arise. Yet even the fastest-dividing cancer cells, which complete mitosis every 18 to 24 hours, do not divide as often as some cells in a normal human embryo do.

True

Cervical cancer, Kaposi sarcoma, and acute T cell leukemia can be caused by __________.

Viruses

mismatch mutations in DNA repair genes

allow other mutations to persist. Inherited in a single-gene fashion and are rare. Cause diverse widespread tumors at a young age

Why is cancer genetic?

because it is caused by changes in DNA, but it is not usually inherited.

The effect of driver mutations is cumulative. One model describes the accumulation of mutations as a cancer forms and progresses as "three strikes" that correspond to three stages:

breakthrough, expansion, and invasion

Increased production of the oncogene's encoded protein ultimately switches on genes that promote mitosis, triggering the cascade of changes that leads to ________.

cancer

Tumor suppressor genes

cause cancer when they are deleted or inactivated. (Recessive)

What are the three cellular processes that cancer disrupts?

cell fate, cell survival, and genome maintenance.

The discovery of the ______________ that control the cell cycle revealed how cancer can begin.

checkpoints

Proto-oncogenes

code for proteins that stimulate normal cell growth and division.

Distinguish between driver and passenger mutations

driver mutation provides the selective growth advantage to a cell that defines the cancerous state. A passenger mutation occurs in a cancer cell, but does not cause or propel the cancer's growth or spread.

The double gene product, called a _______________, activates or lifts control of cell division

fusion protein

Another way that an oncogene can cause cancer is by excessive response to a ____________

growth factor

oncogene

is a gene that causes cancer when it is expressed when it wouldn't be in healthy cells, or is overexpressed. (Dominant)

When proto-oncogenes are transcribed and translated too rapidly or frequently, or perhaps at the wrong time in development or place in the body, they function as _______________.

oncogenes (onco means "cancer")

Drivers can be ___________________________________, and may be generated from rearranged chromosomes.

oncogenes or tumor suppressor genes

More than half of human cancers arise from the mutation or deletion in ___________

p53.

Oncogene activation is associated with a ___________ mutation or a chromosomal ___________ or inversion that places the gene next to another that is more highly expressed (transcribed). Oncogene activation causes a ________-_________-_______. In contrast, a tumor suppressor gene mutation is usually a deletion that causes a__________-___________-_________.

point, translocation, Gain-of-function, Loss of function

How can exome sequencing help to identify a previously unknown cancer gene in a family?

sequencing exomes can reveal genes that are mutant in cancer cells and have a function that could disrupt the cell cycle or DNA repair.

Loss of control over ____________ _________may also contribute to cancer by affecting the cell cycle.

telomere length

Give an example of how the environment contribute to causing cancer?

veggie poor, meaty diet can cause cancer due to amines accumulating which elevate cancer risk. (vegetables release chemicals that activate enzymes that detoxify carcinogenic products of cooked meat called heterocyclic aromatic amines )

Cancer can begin at a cellular level in at least four ways:

■ activation of stem cells that produce cancer cells ■ dedifferentiation ■ increase in the proportion of a tissue that consists of stem or progenitor cells ■ faulty tissue repair