Chapter 7 Cancer Biology Tumor Suppressor Genes
LOH's 3 mechanisms
1. Gene conversion 2. Moitic recombination 3. Nondisjuction 4. Hemizygosity
Retinoblastoma
1. sporadic form no family history 2. famillial form which has a parent who suffered from Rb
Caretakers
DNA maintenance; indirectly controlling the rate at which calls accumulate mutant genes
APC
Facilitates egress of cells from colonic crypts; how cells acquire motility; common in colon cancer; associates with beta-catenin together with two scaffolding proteins this forms a multi-protein complex that brings GSK-3B and B-catenin together which leads to the degradation of Beta- Catenin
Mitotic recombination
a recombination occurring between one of the chromatid arms carrying the wild type Rb allele and a chromatid from the paired chromosome carrying the mutated allele; thought to occur during cell proliferation
NF1
acts as a negative regulator of Ras signaling; behaves closely to Rb thus mutant alleles of this gene gets transmitted through the germ line and acts dominant; converted from heterozygous to homozygous; GAP protein which means it sends Ras to its inactive state: common in neurofibromas
Tumor Suppressor genes
anti growth genes; genes that operate to constrain or suppress proliferation
Gatekeeper
directly control how cells proliferate, differentiate, or die; allowing or disallowing cells to progress through the cell cycle
gene conversion
during DNA replication DNA polymerase switched from normal template to mutated template to a hybrid gene results in LOH
polykaryon
giant mutli-functional cell having one extremely large cytoplasm
Haploinsufficiency
half normal dose of NF1 protein results in a clear and aberrant phenotype
Heterokaryon
hybrid cell which carries 2 genetically distinct nuclei
Syncytium
large cell with a single cytoplasm and two nuclei
Nondisjunction
loss of an entire chromosome due to an inappropriate chromosomal segregation during mitosis
CPG
occurs in the vicinity of a gene promoter it can cause repression of transcription of the associated gene and conversely when methyl groups are removed, transcription of this gene is often re-repressed; important in shutting down TSG
Restriction Fragment Length Polymorphism (RELP)
since the allelic versions of this sequence either permitted or disallowed cleavage by a restriction enzyme known as; these are used to determine if a chromosome under went LOH during the development of tumors. They also depend on the detection of single-nucleotide polymorphism(SNPs) in normal and cancer cells
Hemizygosity
the chromosomal arm is only present in only one copy rather than the usual two copies per cell
pVHL
tumor suppressor gene; in mutated form acts as dominant allele; works best under low oxygen areas it is degraded in high oxygen environments