Neoplasia II #6 (1/26/16) Flashcards
What is Metastasis?
The development of secondary deposits of a tumor in a distant site.
*Considered the hallmark of malignancy (but not always seen)
In general, the ______ and more _____ a tumor is the more likely it is to metastasize.
Larger and more anaplastic
____% of newly diagnosed patients with solid tumors will already have obvious metastases.
30%
What are the 3 pathways of Metastasis?
- Seeding within body cavities - pleura and peritoneum
- Lymphatic spread - usually seen with carcinomas
- Hematogenous spread - usually seen with sarcomas, liver and lungs most often affected.
Most cancer mortality occurs between ____ and ___ years of age.
55-75
What is the proportion of cancer risk that is attributable to environmental sources?
About 2/3rds (65%)
Does cancer increase with age?
yes it frequently does…
_____% of deaths in children under 15 yrs is due to cancer.
10%
What are the 3 broad categories of Genetic predisposition to cancer?
- Inherited cancer syndromes
- Familial cancers
- Defective DNA repair
Inherited cancer syndromes are usually due to what?
A single gene mutation and generally show autosomal dominant transmission. Such as:
- Retinoblastoma
- Familial adenomatous polyposis
- Multiple Endocrine Neoplasia
What are some characteristics of Familial cancers?
- Early age onset
- Tumors arising in two or more close relatives
- multiple or bilateral tumors
- Colon, breast, ovary and brain malignancies have been reported to occur in familial patterns.
What % of cancers have an identifiable heritable basis?
no more than 5-10%
What do Acquired preneopalstic disorders cause?
Increased likelihood of cancer in:
- Persistent regenerative cell replication
- Villous adenomas of the colon
- Leukoplakia of oral or genital mucosa
What is Carcinogenesis?
Nonlethal genetic damage, often due to chemicals, radiation, viruses or inherited mutations, is central to all cancers.
What 3 classes of Normal regulatory genes are often affected in Carcinogenesis?
Protooncogenes (Growth promoting) , Cancer suppressor (growth inhibiting) genes, apoptosis genes.
How do DNA repair genes contribute to cancer development?
They indirectly contribute to cancer development since acquired mutations can be repaired.
T or F, Cancer is a multistep process at both the phenotypic and genetic levels.
True
What is the difference between Prooncogenes and oncogenes?
Prooncogenes are normal functional components of the cell.
Oncogenes encode proteins called oncoproteins that while similar to prooncogene products they lack regulation.
Prooncogenes are transformed to oncogenes by: (2 things)
- Structural mutation of the gene, resulting in an abnormal product.
- Altered regulation of gene expression, resulting in increased production of a normal growth promoting protein.
* This activates oncogenes
All normal cells require ___ stimulation to undergo proliferation.
Growth factor
What does mutation or over expression of Growth factor cause?
It may deliver continuous mitogenic signals and overexertion can make cancer cells which are hyper responsive to even normal levels of GF.
Approx. ____% of all human tumors contain mutated ______.
RAS oncogene
How does Mutant RAS behave differently than good old fashioned RAS?
RAS is normally inactivated quickly, yet mutant RAS remains in its active form stimulation CONSTANT cell proliferation.
In regards to nuclear transcription factors, which gene is most commonly affected?
MYC
What does MYC gene dysregulation cause?
Continuous activation of cyclin-dependant kinases (CDK’s) driving cell to divide.
______ also represses CDK inhibitors.
MYC
CDK’s are regulated by ________.
2 families of CDK inhibitors
What does the product of the RB gene do?
Regulates transcription
What is Knudson’s “Two Hit” hypothesis?
That two mutations “hits” in the genome of a cell are required to induce retinoblastoma.
For retinoblastoma to occur, what must happen?
Both normal alleles of the RB locus must be inactivated (2 hits)
In familial cases, child inherits one _______ of the RB gene and the other Allele is ______.
One defective copy and the other allele is normal.
* When normal RB gene undergoes somatic mutation, tumor develops.
____ is the single most common target for Genetic alterations in human tumors.
TP53
*Homozygous loss of TP53 is found in almost every type of cancer.
Mutations that inactivate both copies of the TP53 gene usually are an __________.
Acquired change in somatic cells
What does TP53 normally do?
It normally acts in the Nucleus to inhabit cell cycle progression.
- When DNA is damaged TP53 accumulates and inhibits cell proliferation and allows time for DNA to repair.
- If repair fails, TP53 activates “cell suicide” apoptosis genes.
What happens with homozygous loss or mutation of TP53?
Your DNA damage will go on unprepared.
These mutations become permanent in diving cells.
Leads to uncontrolled cell division = cancer.
What is Li-Fraumeni syndrome?
Inherited defect of one TP53 allele = 25X more risk of malignancy before age 50.
