Cancer Genetics (15 & 16) Flashcards by Erin Allmer

How do tumors start?

As a single cell with a mutation which proliferates to form a group of similarly abnormal cells (tumors are clonal)

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What is malignancy?

Uncontrolled cell growth characterized by a change in the normal organizational pattern of tissues or cells

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What are the different types of cancer?

Sarcoma

Cardinoma

Hematopoietic/ lymphoid

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What types of cancers are sarcomas?

Affect mesenchymal tissues (bone, cartilage, muscle, fat)

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What types of cancers are carcinomas?

Affect epitheloid tissues

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What types of cancers are hematopoietic/ lymphoid?

Leukemias (WBC from bone marrow)

Lymphomas (WBC from spleen and lymph tissues)

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Name some environmental mutagens?

UV light, asbestos, cigarette smoke, plastics, dyes

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Name 4 hallmarks of cancer?

1- Mutation or loss of genes involved in cell control including growth/ division, proliferation, metabolism

2- Environmental elements may influence mutation

3- mutations may be inherited or acquired

4- chromosome instability

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What are the two types of genes associated with cancer?

1- Proto-oncogenes/ Oncogenes

2- Tumor suppressors

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What are oncogenes involved in?

Upregulating cell growth and proliferation. They are carried by viruses and are associated with disease in animals

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Name 5 viral oncogenes in humans and their associated cancers:

HPV- cervical cancer

EBV- nasopharyngeal cancer, hodgkin lymphoma

HHV-8- Kaposi sarcoma

HTLV-1- T cell leukemia

HTLV-2- Various leukemias

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Generally, what is the function of proto-oncogenes?

Structurally important “housekeeping” genes involved in cell proliferation and development (growth factors, cell surface receptors, intracellular signal transduction, DNA binding proteins, regulation of cell cycle)

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How many mutations are needed for proto-oncogene to promote tumorigenesis?

only one….it is a dominant mutation

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What are the chromosomal findings in CML?

Translocation between chromosome 9 and 22.

There is a juxtaposition of 2 genes that generates a chimeric protein produced with a new function associated with disease

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What is the treatment for CML?

bcr/ abl specific tyrosine kinase inhibitor. It is specific to rearranged chimeric protein

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What are the chromosomal findings in APL?

15; 17 translocation breaking the PML gene on chromosome 15 and the RARA gene on chromosome 17

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What is required for a positive diagnosis of APL?

t(15;17) is clinically diagnostic…seen by FISH

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What is the function of tumor suppressor genes?

Genetic element whose loss or inactivation allows the cell to display an alternate phenotype leading to neoplastic growth

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How many alleles need to be mutated for tumor suppressor genes to promote tumorigenesis?

2…it is a recessive condition

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What are the two general classes of tumor suppressor genes?

1- Gate keepers (suppress tumors by regulating cell cycle or growth inhibition)

2- Caretakers (repair DNA damage and maintain genomic integrity)

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What toes of tumors are mutated tumor suppressors associated with?

Solid tumors

What is an example of a gatekeeper mutation?

Rb1…which functions in regulation of cell cycle (controls the progression from G1 to S)

What chromosome is Rb found on? What is the most common mutation?

Chromosome 13…a deletion is the most common mutation

When is retinoblastoma onset limited to?

Birth to 5 years

Is sporadic or inherited retinoblastoma associated with bilateral retinoblastoma?

Inherited

What secondary cancer is associated with retinoblastoma?

Patients who express retinoblastoma are at risk for a second cancer in their teens...osteosarcoma

If an individual has sporadic retinoblastoma....where did the mutations arise from?

Both mutations are in somatic cells

If an individual has inderited retinoblastoma...where did the mutations arise from?

One was inherited and the other arose spontaneously in somatic cells

What is Knudson's hypothesis?

There is 2 mutations per cell and that sporadic is usually unilateral and inherited is usually bilateral. Also...inheritance sees dominant but it is deceptive and is actually recessive

Name 6 familial cancers:

Breast ovarian cancer Familial polysosis coli Retinoblastoma von Recklinhausen neurofibromatosis Wilm's tumor von Hippel Lindau/ Renal cell cancer

What is Li Fraumeni familial cancer syndrome?

Inherited mutation of p53 50% risk at age 30 and 90% risk at age 70 to develop some type of neoplasm

Where are BRCA1 and BRCA2 found?

BRCA- chromosome 17 (near NF1 and 53) BRCA- chromosome 13 (near Rb1)

Why is mortality in males so high for familial breast cancer?

Because they dont seek help early enough

BRCA genes account for what percentage of breast cancer and what percentage of familial breast cancer?

Total= 5-10% Familial= 80-90%

What is a caretaker mutation?

Inability to repair DNA defects/ mutations that results in an accumulation of abnormal DNA/ genes, increase in genome instability and may lead to mutations of proto-oncogene or tumor suppressor genes

Name some inherited or acquired caretaker mutations?

Fanconi anemia Ataxia telangiectasia Breast Cancer HNPCC Bladder cancer

What are some breakage syndrome?

Fanconi anemia Bloom syndrome Ataxia telangiectasia Xeroderma pigmentosum Cockayne syndrome

What type of inheritance do breakage syndromes have?

recessive inheritance

What are three aspects associated with chromosome instability?

Sister chromatid exchange Triradials Excessive breakage

Which sex has a higher risk of developing colon cancer with inheritance of a mutation?

males

Why can microsatellites be used to study mismatch repair mutations?

microsatellites are prone to slippage, and if a change in these patterns occurs - it can be detected

How is HNPCC diagnosed via microsatellite analyzation?

presence of extra bands confirms the diagnosis

True or false: multiple mutations needs to occur in a single cell for cancer to occur

true - or the clone of that cell

Does the mutations that occur that result in familial polyposis coli include tumor suppressors or proto-onco genes?

both!

In order for karyotyping to be successful in monitoring a disease, what is the requirement?

a baseline for comparison

What are the three chromosomal rearrangements associated with these forms of leukemia: 1. AML-M2 2. AML-M4 3. ALL

1. AML-M2 - Translocation 2. AML-M4 - inversion 3. ALL - translocation

What disease does patients with down syndrome have an increased risk for?

leukemia

Does loss of heterozygosity of a chromosome mean there is only one chromosome present?

nope | -duplication can occur of remaining chromosome

What is a drawback of FISH in monitoring a patient's disease?

only abnormalities specifically being tested will be assessed

When is FISH exceptionally helpful in monitoring transplant patients?

when the recipient and donor are of different sex - want recipient cell line to eventually dissapear - want donor cell line to eventually take over

What percent chance does a carrier have of passing on a mutant allele?

50%

T/F: Risk does not depend on number and degree of affected relatives

falseeee - strong correlation