Tumor Suppressor Genes

__(A)__ critical for triggering degradation of B-catenin. Cells lacking ___(A)__ have shown to have an increase in ___________. Can lead to accumulation of too many chromosomes Loss of this can lead to ________, or incorrect number of chromosomes due to improper advantages in some cells

APC, chromosomal instability (CIN), aneuploidy

__________________ is a tumor suppressor, frequently associated with colon cancer, and is associated with an inherited susceptibility to develop colon polyps. Also called _________________.

Adenomatous polyposis coli (APC), familial adenomatous polyposis (FAP)

_________ gene: ___________ of this gene is associated with breast cancer risk, and to a lesser extent, with ovarian cancer. Found to be inactive in 10-15% of __________ breast carcinomas, but always through methylation, not deletion or mutation

BRCA1, inactivation, sporadic

_______________ contains the replicating stem cells near the bottom--cells further up are more differentiated with specialized functions. Stem cells are protected in the _____ area.

Colonic crypt, crypt

Some regions contain __________, large amounts of CpG areas that are methylated. ____________ tumor suppressor gene was found to be hypermethylated on this in its promoter in solid tumors

CpG islands, RASSF1A

Promoter methylation happens in promoter on ___________ residue.

Cytosine-guanine (CpG)

[Promoter methylation] _______________ adds new methyl group to recently synthesized daughter strands after replication. May involve __________ to the sites of methylated CpGs, which then removes acetate groups from the side chains of AA on _______ molecules in the nearby chromatin (favoring transcription-> inhibiting transcription)

DNA maintenance methylase, histone deacetylases (HDACs), histone

________ is used as a marker for Rb. Located in the ______ chromosomal region. Conduct ______ to identify isoform A/B in normal and tumor tissue in patients

Esterase D, 13q14, electrophoresis

______________ is a _______ cancer associated with the development of benign tumors of the cell sheaths around nerves Occasionally becomes malignant: ____________ Increased risk in tumors of astrocyte lineage in the brain, in the adrenal glands, and in the bone marrow

Neurofibromatosis 1 (NF1), familial, neurofibrosarcomas

____ is used as a newer way to find regions of frequend LOH

PCR

__________ converts one or both prolines on HIF-1a to _____________, which enable the binding of HIF-1a to ___.

Proline hydroxylase, hydroxyproline residues, VHL

Tumor suppressor genes can be identified by mapping _________ (SNPs found within a restriction site)

RFLPs (restriction fragment length polymorphisms)

NF1 i a ________, ___________ is the region that contacts Ras, fits into a cleft, and contributes to GTP hydrolysis. Lack of NF1=Ras is _____

Ras GAP, arginine finger, active

__________ is one of the most well known oncogenes and involves single point mutation. Once activated, can activate multiple pathways in the cell, many of which are involved in cell growth, proliferation, and cell cycle progression

Ras oncogene

______, a tumor suppressor genes implicated in stomach cancer, is almost always inactivated by methylation and not by mutation or deletion

Runx3

________: HDAC inhibitor that reverses deacetylation and thereby reverts the chromatin to a state that favors transcription Treatment of breast cancer cells with this can restore sensitivity to ____

Trichostatin A (TSA), retinoic acid (RA)

__________________ is associated with mutations in VHL tumor suppressor gene

Von Hippel-Lindau Disease (pVHL)

[Adenomatous polyposis coli] _____ is the ligand _____ is the receptor _____ is the proliferation promoting factor

Wnt, Frizzled, B-catenin

Patients of NF1 show "___________", which are areas of hyperpigmentation of skin, and benign region of the ____. ________ that wrap around peripheral axons are probably the source of these growths

cafe au lait, iris, schwann cells

___________________ provided the first clues for presence of tumor suppressor genes

cell fusion experiment

[Adenomatous polyposis coli] when the receptor is not bound with Wnt: Inactive ___________ Active _______ complex with ____, ____, and __(A)___. __(A)__ degraded via ________. No proliferation

disheveled protein (DVL), GSK-3B, axin, APC, B-catenin, proteasome

Methylation is considered ________--heritable trait, but does not alter nucleotide sequence of the DNA

epigenetic

______ retinoblastoma: family history, multiple bilayer tumor Even after treating the tumor, the patient has great increased risk for cancer--usually ______

familial, osteosarcomas

[Cell fusion experiment] when cells growing adjacent to each other in culture are exposed to a _________ agent (_________ or _________), they form a _________ with two nuclei

fusogenic, Sendai virus, polyethylene glycol, heterokaryon

__________: occur during DNA replication (S phase); gene forms a hybrid with the complimentary DNA on the homologous chromosome; leads to loss of heterozygosity

gene conversion

__________ occurs when one allele is missing

hemizygosity

Main function of VHL is to foster destruction of a subunit of a transcription factor called ______________________

hypoxia-inducible factor 1 (HIF-1)

______ is a mutant (activated) or overexpressed version of the proto-oncogene, found in cancer. Mutation on one allele is sufficient to cause cancer

oncogene

____, a tumor suppressor gene, was found to be methylated in 44% of normal bronchial epithelial cells cultured from current and former smokers

p16

[Target genes that HIF-1 activates] ____: stimulates cells important for blood vessels

platelet derived growth factor (PDGF)

___________: type of heterokyron with more than two nuclei; usually cannot proliferate

polykaryons

____________: mechanism for inactivation of tumor suppressor genes in addition to LOH Gene sequences appear normal but inactivates gene at _______ by ______.

promoter methylation, promoter, methylation

_______ is a normal cellular gene that is associated with cancer only if it is improperly activated (usually by overexpression, mutation, or gene translocation)

proto-oncogene

_____________: first tumor suppressor genes discovered; loss of chromosomal material at _______

retinoblastoma (Rb), 13q14

_________: potent inducer of cell cycle arrest in many epithelial cells In many cases, the gene for _________, which encodes this receptor is silenced due to methylation-> unresponsive

retinoic acid (RA), RARB2

Methylation specific PCR: treatment with _______ under _____ conditions convert ________ cytosines to _______, while leaving ________ Cs untouched

sodium bisulfite, alkaline, non-methylated, uracil, methylated

_______ retinoblastoma: no family history; single unilateral tumor

sporadic

[colonic crypt] Enterocyte stem cells encounter Wnt factors released by _______ cells near the bottom of the crypt-> keeps ______ level high in cells-> held in stem cell like states

stromal, B-catenin

[Target genes that HIF-1 activates] _____: stimulates growth of a variety of cell types including epithelial cells

transforming growth factor alpha (TGF-a)

________only causes cancer if it is inactivated or deleted. Mutations must occur on both alleles to cause cancer

tumor suppressor gene

VHL tags HIF-1a by _________ and targets it for destruction (requires ATP)

ubiquitylation

[Target genes that HIF-1 activates] _____: causes growth of endothelial, or blood vessel, cells

vascular endothelial growth factor (VEGF)