Genetic alterations associated with cancer
a gene and cancer technology, applied in the field of gene alterations associated with cancer, can solve the problems of limited homozygous (polymorphism-based techniques) and achieve the effect of reducing the number of homozygous
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example 1
[0095]This example describes the identification of genes in a 2 MB region at 3q26.3 region. Increased copy number of this region is correlated with ovarian cancer.
[0096]CGH studies have identified DNA copy number abnormalities at 3q25-26 associated with ovarian tumors (Iwabuchi et al., Cancer Research 55:6172-8180 (1995)). To physically map the 3q26 region, a number of yeast artificial chromosome (YAC), P1, and cosmid clones that were known to genetically map to the region were physically mapped to the 3q region. Several yeast artificial chromosome (YAC) and P1 clones known to genetically map to this region were physically mapped using FISH and fractional length analysis. Clone positions were reconfirmed by PCR using STSs specific to the region. Clones were then picked according to their physical map position and hybridized onto interphase cells of ovarian cancer, breast cancer, and melanoma cell lines, as well as nuclei of paraffin-embedded ovarian tumors. One of the P1 clones and ...
example 2
[0111]This example shows that PIK3CA expression is increased in ovarian cancers as a result of the PIK3CA copy number increase.
[0112]As noted above. PIK3CA is an attractive as a candidate oncogene in ovarian cancer because of the broad range of cellular functions that are modulated by increased PI3-kinase activity (Cantley et al. J. Am. Soc. Nephrol. 5:1872-1881 (1995), Fry Biochi. Biophys. Ada 1226:237-268 (1994)). These include increased including cell proliferation, accelarated glucose transport and catabolism (Frevert et al. Mol Cell Biol 117:190-198 (1997),Tsakiridis et al., Endocrinology 136:4315-4322 (1995), altered cell adhesion (Chen et al. J. Biol Chem. 269:31229-31233 (1994), Kinashi et al. Blood 86:2086-2090 (1995)) and altered vesicle transport (Joly et al. J. Biol. Chem. 270:13225-13230 (1995) and Dudek et al. Science 275:661-665 (1997)).
[0113]Increased PI-kinase activity also is implicated in abrogating apoptosis. For example, neuronal survival is increased after acti...
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