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Common Fragile Sites and Cancer: Targeted Cloning by Insertional Mutagenesis
Author(s) -
BÜTTEL ISABEL,
FECHTER ANNE,
SCHWAB MANFRED
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1322.002
Subject(s) - insertional mutagenesis , mutagenesis , cloning (programming) , genetics , chromosomal fragile site , cancer , biology , computational biology , mutation , gene , computer science , genome , chromosome , programming language
A bstract : Genetic instability is an important facet of carcinogenesis and oncogenesis, generating chromosomal variability and extensive intratumor heterogeneity. Common fragile sites are predetermined chromosomal breakage regions. Experimentally, they can be demonstrated as site‐specific gaps or breaks seen on metaphase chromosomes under conditions of replicative stress. They have been known for many years as a chromosomal expression of genetic instability and have been implicated to have a causative role in cancer. However, common fragile sites still remain enigmatic intrinsic parts of human chromosomes, and the DNA sequences at most of the fragile sites have noot been identified so far. The idea of genetically tagging fragile site DNA by insertional mutagenesis through an exogenous marker gene has provided a platform for the efficient targeted cloning of a substantial number of common fragile sites.