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Purpose: Genetic changes in sporadic ovarian cancer are relatively poorly characterized compared with other tumor types. We have evaluated
the use of high-resolution whole genome arrays for the genetic profiling of epithelial ovarian cancer.
Experimental Design: We have evaluated 31 primary ovarian cancers and matched normal DNA for loss of heterozygosity and copy number alterations
using 500K single nucleotide polymorphism arrays.
Results: In addition to identifying the expected large-scale genomic copy number changes, >380 small regions of copy number gain or
loss (<500 kb) were identified among the 31 tumors, including 33 regions of high-level gain (>5 copies) and 27 homozygous
deletions. The existence of such a high frequency of small regions exhibiting copy number alterations had not been previously
suspected because earlier genomic array platforms lacked comparable resolution. Interestingly, many of these regions harbor
known cancer genes. For example, one tumor harbored a 350-kb high-level amplification centered on FGFR1 and three tumors showed regions of homozygous loss 109 to 216 kb in size involving the RB1 tumor suppressor gene only.
Conclusions: These data suggest that novel cancer genes may be located within the other identified small regions of copy number alteration.
Analysis of the number of copy number breakpoints and the distribution of the small regions of copy number change indicate
high levels of structural chromosomal genetic instability in ovarian cancer.