Neoplasia 2- Metastasis Flashcards by asw asw

what is metastasis?

Metastasis is the development of secondary deposits of a tumor in a distant site

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___________ is the “hallmark of malignancy”

metastasis

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T/F: Some types of cancer metastasize more readily than others

true

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In general, the ________ and more _______ a tumor is, the more likely it is to metastasize

larger and more anaplastic (less differentiated)

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what are the 3 mechanisms for metastasis?

Seeding within body cavities
Lymphatic spread
Hematogenous spread

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carcinomas usually metastasize through what mechanism?

lymphatic spread

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how do most sarcomas metastasize?

Hematogenous spread

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what organs are most effected by hematogenous spread?

Liver and lungs most often affected.

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___________ Often provides clues as to the etiology (cause) of or contributing factors to cancer development

epidemiology

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Proportion of cancer risk attributable to environmental sources estimated to be roughly _______

2/3rds (65%)

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most cancer mortality occurs between what ages?

55 and 75 years of age

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what are the 3 broad categories of genetic predisposition to cancer?

a. Inherited cancer syndromes
b. Familial cancers
c. Defective DNA repair

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_____________ cancer syndromes are usually due to a single gene mutation

Inherited cancer syndromes

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what type of genetic transmission is usually seen in inherited cancer syndromes?

autosomal dominant

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give 3 examples of inherited cancer syndromes

1) Retinoblastoma
2) Familial adenomatous polyposis
3) Multiple endocrine neoplasia (MEN)

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what are the characteristics of familial cancers?

early age at onset

tumors arising in two or more close relatives of the index case

multiple or bilateral tumors

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what types of malignancies have been linked to familial inheritance patterns?

Colon, breast, ovary and brain malignancies

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what inherited trait causes xeroderma pigmentosum?

Autosomal recessive syndromes of defective DNA repair

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Approximately ____% of newly diagnosed patients with solid tumors will present with metastases, while another ____% will have occult (too small to be detected clinically) metastases at the time of diagnosis.

30%

20%

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T/F: Probably no more than 20-30% of all human cancers have an identifiable heritable basis

FALSE

its 5-10%

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Acquired Preneoplastic Disorders (APD’s) will increase the LIKELIHOOD of what forms of cancers?

Persistent regenerative cell replication
Villous adenomas of the colon
Leukoplakia of oral or genital mucosa

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what does Carcinogenesis refer to?

Nonlethal genetic damage (that causes cancer)

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what types of cellular damage result in carcinogenesis?

chemicals, radiation, viruses or inherited mutations

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what 3 classes of normal regulatory genes are often affected by non-lethal genetic damage?

1) protooncogenes (growth promoting)
2) cancer suppressor genes (growth inhibiting)
3) apoptosis genes

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____________ genes will indirectly contribute to cancer development since acquired mutations can’t be repaired

DNA repair genes

Carcinogenesis is a multi-step process at both the ___________ and __________

phenotypic and genetic levels

T/F: Protooncogenes are a normal functional component of the cell

true

Oncogenes encode proteins called ___________

oncoproteins

what is the difference between the proteins made from protoonconogens, and those of onconogenes?

the onconoproteins lack REGULATION

Protooncogenes are transformed to oncogenes by what 2 processes?

1) Structural mutation of the gene | 2) Altered regulation of gene expression

__________ mutations of a gene result in an abnormal product

structural

Altered regulation of gene expression results in what?

results in increased production of a normal growth-promoting protein

what are 2 examples of growth-factor mutations that can cause cancer?

1) Glioblastoma - platelet-derived growth factor (PDGF) | 2) some Sarcomas - transforming growth factor-alpha (TGF-α)

what class of growth-factor receptor is linked to cancer when mutated?

epidermal growth factor receptor family ERBB-1 and ERBB-2

____________ (a receptor) is overexpressed in 80% of Squamous cell carcinomas (SSCa's) of the lung

ERBB-1 (EGF receptor)

an elevation of ERBB-2 (HER2/NEU receptor) is amplified in some _______ cancers, which correlates to poorer prognosis

breast

Mutant receptor proteins deliver continuous ________ signals

mitogenic

Over-expression of growth factor receptors makes cancer cells hyperresponsive to what?

normal levels of growth factors

several oncoproteins mimic the functions of normal cytoplasmic ______________ proteins

signal-transducing

approximately 30% of all human tumors contain what mutated gene?

contain mutated RAS oncogene

_______ is the most commonly mutated proto-oncogene

RAS

In the normal situation, activated RAS (resulting from exchange of GDP for GTP) turns on what?

downstream regulators of proliferation

Normally inactivated quickly, mutant RAS remains in its active form..... what effect does this have?

stimulates constant cell proliferation | it is a growth signal transducer that never turns off

With mutated ras, the ras proteins bind the ________, but GTPase activity is not accentuated

GAP's (GTPase-activating proteins)

how is RAS inactivated?

inactivated by hydrolysis of GTP (this is enhanced by binding of RAS to GAP) ``` GTP= active GDP= inactive ```

the ____ gene is the most commonly affected Nuclear transcription factor gene

MYC

MYC gene dysregulation leads to ____________

overexpression

mutated MYC, resulting in overexpression, will have what effects in the cell?

leads to continuous activation of cyclin-dependent kinases (CDKs)

the result of continuously activated CDK's will cause what cellular response?

drives cell to divide indefinitely

what is cyclin D1?

a gene whose product drives cells into the cell cycle

what is a type of cancer linked to MYC onconogenes?

Burkitt’s lymphoma

along with activating CDK enzymes, MYC will also represses ________

CDK inhibitors

Orderly progression of cell cycle is orchestrated by CDK’s following activation by binding to ______

cyclins

Overexpression of _______ is seen in a variety of tumors, including melanoma, lymphoma and esophageal carcinomas

CDK's

the products of __________ genes inhibit cell proliferation

tumor-supressing genes

what is Knudson’s “two-hit” hypothesis?

Two mutations (“hits”) in the genome of a cell required to induce retinoblastoma - you need BOTH alleles of the RB genome to be mutated

T/F: while protooncogenes stimulate cell growth, suppressor genes inhibit cell proliferation

true

how is Knudson's "two-hit" hypothesis related to the familial inheritance of retinoblastoma?

- kids inherit ONE mutant allele of the RB gene | - this VASTLY increases likelihood of BOTH RB genes becoming mutated

The Rb gene product (pRb) is a ___________ protein that is a key player in the regulation of the cell cycle

transcription regulatin protein (DNA-binding)

The ___________________ gene is the single most common target for genetic alteration in human tumors

The TP53 tumor suppressor gene

___________ loss of TP53 is found in virtually every type of cancer

Homozygous

Li-Fraumeni syndrome is caused by what?

the familial inheritance of ONE aberrant TP53 gene - they start with 1 mutated copy, making the likelihood of both being mutated much higher

how does TP53 normally work?

TP53 works to slow down DNA replication when mutations have affected the DNA - normally works in the NUCLEUS to inhibit cell cycle progression

under normal circumstances, if DNA repair mechanisms fail, TP53 activates _______ genes

“cell-suicide” (apoptosis)

people suffering from _________ syndrome have a 25x increased risk for malignancy before age 50

Li-Fraumeni syndrome | inherited defect of one TP53 allele