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Genetic Changes in Neoplasia
Genetic Changes in Neoplasia Flash Cards
98
Biology
Undergraduate 2
06/12/2012
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Term
Everything to do with cancer initiation and it's progression comes down to the __________.
 Definition
1) Gene
Term
All cell types in the body originate from a __________ __________ or __________.
 Definition
1) Fertilized ovum
2) Zygote
Term
Cells divide and __________.
 Definition
1) Differentiate
Term
True or False: All cells have the same genetic information?
 Definition
1) True
Term
What makes cells of one organ different from those of another is the type of __________ expressed; different __________ produce specialized cell types.
 Definition
1) Gene
2) Genes
Term
Only a small number of genes are expressed in __________ life.
 Definition
1) Postnatal
Term
True or False: A large number of genes are expressed in postnatal life.
 Definition
1) False
Term
Both the rate of cell __________ and process of cell __________ cease once appropriate numbers and types of cells are formed.
 Definition
1) Reproduction
2) Differentiation
Term
True or False: Only the process of cell differentiation ceases once appropriate numbers and types of cells are formed; the rate of cell reproduction increases.
 Definition
1) False
Term
The more specialized a cell becomes the more likely it is to lose its ability to undergo __________.
 Definition
1) Mitosis
Term
True or False: The more specialized a cell becomes, the more likely it is to lose its ability to undergo mitosis.
 Definition
1) True
Term
In certain __________, cell renewal continues through life.
 Definition
1) Tissues
Term
True or False: In certain tissues, cell renewal continues through life.
 Definition
1) True
Term
__________ cell remain incompletely differentiated (__________) throughout life; quiescent until needed for cell replenishment.
 Definition
1) Stem
2) Dedifferentiated
Term
In some tissues, __________ __________ cells have a limited capacity for self-renewal (terminally differentiated) and restricted to producing a single cell type.
 Definition
1) Parent progenitor
Term
__________ cells are able to become any tissue including the placenta.
 Definition
1) Totiplotent
Term
Only __________ cells are totipotent: able to become any tissue including the __________.
 Definition
1) Morula
2) Placenta
Term
Pluripotent cells come from the inner cell mass within the __________ and cane become any tissue in the body except the __________.
 Definition
1) Blastocyst
2) Placenta
Term
__________ cells come from the inner cell mass within the blastocyst and can become any tissue in the body except the placenta.
 Definition
1) Pluripotent
Term
__________ cells form multiple but limited numbers of lineages.
 Definition
1) Multipotent
Term
__________ cells give rise to a single cell type.
 Definition
1) Unipotent
Term
True or False: All cells differentiate.
 Definition
1) False
Term
Not all cells __________: at each level stem cells remain in an uncommitted state, retaining ability to __________ when needed.
 Definition
1) Differentiate
2) Differentiate
Term
__________ are normal genes that code for proteins that regulate cell growth and differentiation.
 Definition
1) Proto-oncogenes (c-onc0
Term
What is the role of proto-oncogenes (c-onc)?
 Definition
1) Code for proteins
2) Regulate cell growth
3) Regulate differentiation
Term
__________ are genes that are mutated or expressed at high levels; they help to turn normal cells into tumor cells.
 Definition
1) Oncogene (onc)
Term
True or False: Oncogenes are genes which are mutated and expressed at high levels and turn normal cells into tumor cells.
 Definition
1) True
Term
What do oncogenes do?
 Definition
1) Mutated gene expressed at high levels which turn normal cells into tumor cells.
Term
__________ __________ __________ or anti-oncogenes are genes that protect cells from excessive proliferation and prevent the one step path to cancer.
 Definition
1) Tumor suppressor gene (TSG)
Term
True or False: TSGs are responsible for promoting cancer.
 Definition
1) False
Term
Cancer transformation requires a __________ __________.
 Definition
1) Multistep program
Term
__________ __________ changes transform normal cells into cancer cells.
 Definition
1) Nonlethal genetic
Term
What are 4 types of nonlethal genetic changes that can transform a normal cell into a cancer cell?
 Definition
1) Chemicals
2) Radiation
3) Viruses
4) Inherited factors
Term
Nonlethal genetic changes transform a __________ (regulated) to a __________ (continuous)
 Definition
1) Proto-oncogene
2) Oncogene
Term
The inactivation of __________ __________ __________ leads to unregulated growth.
 Definition
1) Tumor suppressor genes
Term
Mitosis in a mutated cell is rapid (__________) in stark contrast to a normal cell (__________)
 Definition
1) 0.07 hours
2) 0.5 hours
Term
In sporadic __________, the zygote is genetically wild type at Rb locus.
 Definition
1) Retinoblastoma
Term
In sporadic retinoblastoma, the zygote is genetically wild type at what locus?
 Definition
1) Rb
Term
In the __________, retinoblastoma development requires two successive mutations of both __________ gene copies to yield the same outcome: cell poised to proliferate into tumor mass.
 Definition
1) Retina
2) Rb
Term
In __________ retinoblastoma, the sporadic disease involves the production of a __________ tumor in one eye or the other.
In __________ retinoblastoma, the familial disease involves production of tumors in __________ eyes.
 Definition
1) Unilateral
2) Single
3) Bilateral
4) Both
Term
__________ __________ __________ can occur through elimination of wild type Rb gene copies at __________/__________.
 Definition
1) Loss of Heterozygosity (LOH)
2) G2 / M
Term
In retinoblastoma, once the __________ allele is mutated, mitotic recombination can lead to __________.
 Definition
1) Rb
2) LOH
Term
In retinoblastoma, once the Rb allele is mutated, what finally leads to LOH?
 Definition
1) Mitotic recombination.
Term
Genetic material is exchanged between two homologous chromosomes through genetic __________ __________ which is the __________/__________ in the cell cycle.
 Definition
1) Crossing over
2) G2 / M
Term
Segregation of chromatids may yield daughter cells which:
1) Both retain __________ at Rb locus or
2) Two daughter cells where one is __________ __________ at Rb locus while other is __________ __________ type.
 Definition
1) Heterozygosity
2) Homozygous mutant
3) Homozygous wild
Term
Certain genetically inherited conditions carry predisposition to cancer involving interaction between __________ and __________ factors and faulty __________ __________ mechanisms.
 Definition
1) Genetic
2) Environmental
3) DNA repair
Term
__________ __________ is an autosomal recessive disease in which the skin is extremely sensitive to sunlight; and incidence of skin cancer approaching 100% and frequent neurological deficiency.
 Definition
1) Xeroderma pigmentosum
Term
Xeroderma pigmentosum is an __________ __________ disease which has extreme sensitivity to sunlight.
 Definition
1) Autosomal recessive
Term
What are the risk factors associated with xeroderma pigmentosum?
 Definition
1) Extreme sensitivity to sunlight
2) Incidence of skin cancer approaching 100%
3) Frequent neurological deficiency
Term
A patient suffering from XP as severe and extensive __________ in all areas of sun-exposed skin.
 Definition
1) Lesions
Term
Lesions can develop into __________ and __________ cell carcinomas as well as __________.
 Definition
1) Squamous
2) Basal
3) Melanomas
Term
Tumor development in XP is __________x greater than in the general population.
 Definition
1) 1000
Term
Patients suffering from XP exhibit skin cancer far earlier (around __________ years) than the general population which appears around __________ years.
 Definition
1) 10
2) 60
Term
In XP virtually all who develop skin cancers have already done so by the time they reach __________ years.
 Definition
1) 25
Term
The XP gene encodes the __________-__________ __________ system
 Definition
1) Nucleotide-excision repair
Term
The NER system is encoded by __________ XP genes.
 Definition
1) 8
Term
The NER system is unable to repair __________ generated genetic damage due to an incorrect __________ (sugar, base, phosphate) incorporation; __________ dimers aren't recognized.
 Definition
1) UV
2) Nucleotide
3) Pyrimidine
Term
__________ of XP patients are also susceptible to increased risk by other diseases; mostly __________.
 Definition
1) 18%
2) Neurological
Term
__________ damage is the most important legion requiring repair by NER machinery.
 Definition
1) UV
Term
True or False: XP was the first of many cancers to be shown as an inherited defect in DNA repair machinery.
 Definition
1) True
Term
Hereditary non-polyposis colon cancer is responsible for __________-__________ of colon cancers.
 Definition
1) 2-3%
Term
A subclass of which cancer has increased susceptibility to endometrial, stomach, ovarian, and urinary tract infections?
 Definition
1) Hereditary non-polyposis colon cancer (HNPCC)
Term
HNPCC has increased susceptibility to what infections?
 Definition
1) Endometrial
2) Stomach
3) Ovarian
4) Urinary tract
Term
Adenoma to carcinoma progression takes how long?
 Definition
1) 8-10 years
Term
HNPCC patients inherit one or more defective __________ __________ mismatch-repair alleles; __________ of patients who inherit defective gene develop HNPCC
 Definition
1) Autosomal dominant
2) 80%
Term
Cancer progression in HNPCC results from germ line mutations in genes encoding two __________ proteins: __________ (recognized mismatches) and __________ (signals repair enzymes).
 Definition
1) MMR
2) MSH2
3) MLH1
Term
What is the role of MSH2 and MLH1?
 Definition
1) MSH2 recognizes autosomal dominant mismatches
2) MLH1 signals repair enzymes to such mismatches
Term
__________ __________ __________ machinery prevents repair of DNA replication mistakes.
 Definition
1) Mutant mismatch repair (MMR)
Term
__________ __________ is a colonic cancer in which the TGF-beta type II receptor has mutated, losing two of its __________ and forcing coding section out of normal reading frame.
 Definition
1) Microsatellite instability
2) As
Term
Microsatellite instability results in nonfunctional truncated __________-__________ __________ receptor protein.
 Definition
1) TGF-beta RII
Term
In many cases, the MMR defect is found in __________ rather than __________ cancers.
 Definition
1) Sporadic
2) Familial
Term
MMR genes can be rendered defective by __________ mutation which methylates the __________ region which controls gene transcription or trnascriptional silencing.
 Definition
1) Somatic
2) Promoter
Term
__________ __________ is responsible for the lion's share of defective MMRs in specific tumors.
 Definition
1) Promoter methylation
Term
__________ __________ is an important mechanism of gene regulation.
 Definition
1) Epigenic inheritance
Term
Methylation of __________ in gene sequences prevents binding of gene regulatory sequences.
 Definition
1) Cystines
Term
Epigenic inheritance inactivates a gene's expression or __________ gene that regulates it by preventing __________ __________ from initiating transcription.
 Definition
1) Promoter
2) RNA polymerase
Term
True or False: Epigenic inactivation can be inherited.
 Definition
1) True
Term
Epigenic inactivation of __________ contributes to cancer formation.
 Definition
1) TSGs
Term
About __________ of sporadic gastric, colorectal, and endometrial tumors show promoter methylation.
 Definition
1) 15%
Term
Partial loss of __________ function leads to karyotypic abnormalities.
 Definition
1) BRCA2
Term
Mutant germ line alleles of BRCA1 / BRCA2 confer inborn susceptibility to which two cancers?
 Definition
1) Breast
2) Familial ovarian
Term
BRCA1 / BRCA2 confer inborn susceptibility to what percent of familial ovarian cancers?
 Definition
1) 70-80%
Term
The inability to repair homologous chromosome lesions leads to maintenance of breaks - leading to __________ __________.
 Definition
1) Non-homologous fusions
Term
Unusual chromosomal fusions occur as a result of improper repair of __________ __________ breaks.
 Definition
1) DS DNA
Term
The ability of daughter cells to separate from one another completely during __________ is affected since still attached to spindle microtubules; leads to __________ catastrophe and __________ __________.
 Definition
1) Cytokinesis
2) Mitotic
3) Cell death
Term
The __________ protein contributes to the maintenance of normal DNA and chromosomal structure by acting as __________ to assemble a cohort of other DNA repair proteins into large physical complexes.
 Definition
1) BRCA 2
2) Scaffolds
Term
What is the role of BRCA 2?
 Definition
1) Contributes to maintenance of normal DNA and chromosomal structure
2) Acts as a scaffold to assemble a cohort of other DNA repair proteins into large physical complexes.
Term
What are the large physical DNA repair complexes assembled by the BRCA 2 protein responsible for?
 Definition
1) Aiding in the repair of DS DNA breaks.
Term
What detrimental effects occur with the loss of BRCA1 and BRCA2?
 Definition
1) Disables certain cell cycle checkpoints that normally respond to damaged DNA
2) Compromises process of homologous recombination
3) compromises process of homology-directed repair
Term
Alterations of chromosome structure can occurs as accidents of __________.
 Definition
1) Mitosis
Term
Changes in chromosome number create a condition called __________ __________.
 Definition
1) Chromosomal instability
Term
Cancer cells show marked defects including:
 Definition
1) Multiple centrosomes at interphase which may result in mitotic spindles that have multiple poles rather than the two seen in normal cells
Term
Inheriting a __________ point mutation can predispose a family to a variety of tumors.
 Definition
1) p53
Term
Li-Fraumeni syndrome is a rare __________ __________ disease for point mutation __________.
 Definition
1) Autosomal dominant
2) p53
Term
Mutant __________ are transmitted through the germ line; __________ are usually not.
 Definition
1) TSGs
2) Oncogenes
Term
Mutations that yield activated __________ usually act at the cellular level as dominant alleles.
 Definition
1) Oncogenes
Term
Mutant __________ perturb the behavior of individual cells in the developing embryo, disrupting normal tissue development.
 Definition
1) TSG
Term
Most mutant TSG alleles are __________ at the cellular level; their presence in most embryos will not be apparent.
 Definition
1) Recessive
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