Genomic instability and XXXX .

@entity4310 @entity124 @entity5 @entity19 @entity377 @entity3207 @entity14 @entity1344 @entity1129 @entity2008 @entity10673 @entity11807
Tumorigenesis can be viewed as an imbalance between the mechanisms of cell-cycle control and mutation rates within the genes. Genomic instability is broadly classified into @entity124 ( @entity124 ) associated with mutator phenotype, and @entity1344 ( @entity1344 ) recognized by gross @entity2008 . Three intracellular mechanisms are involved in DNA damage repair that leads to mutator phenotype. They include the @entity377 excision repair (NER), base excision repair (BER) and mismatch repair (MMR). The @entity1344 pathway is typically associated with the accumulation of mutations in @entity5 suppressor genes and oncogenes. Defects in DNA MMR and @entity1344 pathways are responsible for a variety of @entity4310 predisposition syndromes including @entity14 ( @entity14 ), @entity10673 , @entity1129 , and @entity11807 . While there are many genetic contributors to @entity1344 and @entity124 , there are also epigenetic factors that have emerged to be equally damaging to cell-cycle control. Hypermethylation of @entity5 suppressor and DNA MMR gene promoter regions, is an epigenetic mechanism of gene silencing that contributes to tumorigenesis. Telomere @entity3207 has been shown to increase genetic instability and @entity5 formation in @entity19 , underscoring the importance of telomere length and telomerase activity in maintaining genomic integrity. @entity19 models have provided important insights for discovering critical pathways in the progression to @entity5 , as well as to elucidate cross talk among different pathways. This review examines various molecular mechanisms of genomic instability and their relevance to @entity5 .
