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UNIT 7 > MCP 15&16 > Flashcards

Flashcards in MCP 15&16 Deck (43):

Define tumor

-overgrowth of cell material, can be solid or dispersed
-clonality - all the cells typically originate from one mutated cell line
-can be benign or malignant


Define benign

-milder, usually harmless, non-progressive disease does not metastasize


describe clonal

- tumors generally start as a single cell with a mutation which proliferates to form a group of similarly abnormal cells


Define malignancy

uncontrolled cell growth characterized by a change in the normal organization pattern of tissues or cells
-karyotypic changes, metastasis


Define metastasis

when cells become invasive or migrate to another site. When they move they retain the original cell morphology. Therefore a tumor in the liver that was founded by breast cancer cells is still called breast cancer


Define cancer

-malignant tumor or potentially unlimited growth that expands locally by invasion and systemically by metastasis -> overgrowth of cell material and clonal


How is a primary cancer in a secondary location classified?

- classified by its primary location type


Name some environmental factors that affect cancer incidence

UV light, asbestos, cigarette smoke, plastics dyes, red dye #3
- cancer most likley a combination of environmental and genetic factors


Hallmarks of cancer

-mutations or loss of genes involved in cell control including growth/division, proliferation metabolism
-environmental elements may influence mutation
-mutations may be inherited or acquired
-chromosome instability (gain or loss of chromosomes)



-a dominantly acting gene involved in unregulated cell growth and proliferation
-carried by viruses
-associated with disease in animals
H-ras-harvey rat sarcoma
sis-simian sarcoma virus
abl-abelson murine leukemia virus


What are the oncogenes found in humans?

viral oncogenes in humans
-HPV -cervical cancer E6 and E7
-EBV- nasopharyngeal cancer, hodgkin and burkitt lymphoma
-HHV 8 - kaposi sarcoma
-HTLV -1- T cell leukemia
-HTLV-2 various leukemias
-mutation of other proto oncogenes


Define proto-oncogenes

-critically important housekeeping genes that are present throughout the human genome and in their native state are not associated with diseases
-present throughout the genome and have been mapped to nearly all chromosomes


List some of the functions of proto-oncogenes

-growth factors
-cell surface receptors
-intracellular signal transduction
-DNA binding proteins (transcription)
-regulation of cell cycle


Describe what happens when proto-oncogenes go haywire

-mutation (translocation, amplification, point mutation) can result in "activation" of a proto-oncogene
-this may change gene regulation, gene transcription or a protein product generating alterations to cell growth, proliferation or differentiation
-can lead to tumorigenesis
-gain of function mutation
-dominant - only need one mutation


what is clinically diagnostic of APL

- translocation of 15 and 17 is considered clinically diagnostic
- because of the need of hasty results FISH is generally performed first and then karyotype analysis


Tumor suppressor

-genetic element whose loss or inactivation allows the cell to display an alternate phenotype leading to neoplastic growth
-oncogenetic potential when gene activity is lose
-true recessive


Name and specify the two types of tumor suppressor gene types

gate keepers-> suppress tumors by regulating cell cycle or growth inhibition
caretakers - repair DNA damage and maintain genomic integrity -> effect is indirect via the accumulation of errors in the cells


List some normal functions of tumor suppressor genes

- cell to cell interactions
-regulation of growth inhibitory substances
-cell differentiation
-chromosome repair
-cell proliferation


What type of cancers do tumor suppressor genes have the biggest influence over?

solid tumors!
- difficult to culture


Name a classic gate keeper disease

Rb 1 functions in regulation of cell cycle
- controls progression from g1 to s
- loss of function eliminates an important mitotic checkpoint resulting in uncontrolled growth



An example of a tumor suppressor is seen in this disease which is a tumor of the retinoblastoma (immature cells of the retina). Once retinoblastoma mature to retinal cells the target tissue of this disease is gone and the disease does not occur after age of 5.
- 1/20,000
- prenatal to age 5
-unilateral usually sporadic
- bilateral usually inherited
- secondary cancer Osteosarcoma
Severe cases require enucleation
Some may be treated by laser surgery


Knudson's two hit hypothesis

Two mutations in same cell
Sporadic usually unilateral
Inherited usually bilateral
Appearance of dominance but truly recessive


Earlier age of cancer onset

If a person inherits one mutation his/her disease will occur early in life (birth to 30) since it generally will not take a long time for the second mutation to occur and initiate carcinogensis


Later age of onset of cancer

If not mutation is inherited two mutation must occur sporadically to initiate the abnormal clone. This will require more time and these cancers typically occur in the later decades of life


Li fraumeni

-familial cancer syndrome
- multiple neoplasia
- increased risk of cancer 50% at age 30, 90% at age 70
- inherited mutation of p53 ( lose checkpoint of DNA damage)


Where are BRCA 1 and BRCA 2 located ?

BRCA 1 -> chromosome 17 (near NF1 and p53)
BRCA20 -> chromosome 13 (near rb1)


Why is the mortality higher in males with breast cancer?

Higher bc people don't think it can happen to men and it takes longer for them to seek care



80-90% of familial breast cancer
5-9% of all breast cancer
Multiple mutations
Increased risk for male breast cancer as well
Increased risk in Ashkenazi Jewish population
Counseling patients is critical


Caretaker mutations

Inability to repair DNA defects mutations
- accumulations of abnormal DNA genes
-Increased risk of genome instability
-May lead to mutation of proto-oncogene tumor suppressor genes
Inherited or acquired


List some examples of breakage syndromes

- fanconi anemia
- Bloom syndrome
- ataxia telanglectasia
- xeroderma pigmentosum
- cockayne syndrome


What four features do breakage syndromes share?

1. Recessive inheritance
2. Chromosome instability
3. Defective DNA repair machinery
4. Susceptibility to cancer



Replication has resulted in a Y shaped or fork structure


Hereditary nonpolyposis colon

2-4% of hereditary colon cancer
90% lifetime risk or males who inherit one mutation
70% lifetime risk for females who inherit one mutation
-40% risk of endometrial cancer
-10-20% risk of urinary tract cancer
-10-20% risk of ovarian cancer


Mismatch repair

If an error occurs during replication it is detected by checking enzyme excised along with adjacent bases and missing portion is filled in correctly and ligated back to existing DNA


What happens when mismatch repair goes wrong?

Two cell lines, one with the appropriate sequence and one with the incorrect, mutated sequence



Repeats of 2, 3, or 4 nucleotides -> highly polymorphic in population and can be in DNA analysis because subject to replication error use to slippages
Also mutations in mismatch pairs can alter total number of repeats
For example change in pattern of repeats can be indicative of mutation used for HNPCC diagnosis


Cancer evolution

Progression from normal to cancer cells requires a combination of environmental and genetic effects
Many different mutations occur but the key principle is that these mutations must occur in the same cell


Define clonality

A normal cell may have a single mutation which proliferates and generates an abnormal clone this is an acquired change in a limited number of cells. Further chromosomal changes may modify the karyotype and produce additional clones - karyotype analysis can be used to monitor the presence and evolution of clones


Define karyotype analysis

Change over time in the karyotype due to acquisition different mutations. Generally increasing complexity and number of chromosome abnormalities are associated I with poorer is possible to use chromosome abnormalities to follow patient from diagnosis to remission and relapse.


Define constitutional findings

Original DNA and chromosome complement that is the foundation for the genetic constitution in all cells of the body
Originate in zygote


Acquired anomalies

A change which has occurred in the constitutional DNA or karyotype - usually present in a single cell line or clone


Define loss of heterozygosity

Apparent homozygosity or hemizygosity in a tissue which demonstrates heterozygosity constitutionally
Demonstrates the importance of having a baseline



- in some instances there is a direct correlation between particular chromosomal finding and the course of the disease
- knowing that information may aid in determine the type of treatment utilized
- a more resistant disease may be treated more aggressively