High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications.
OBJECTIVE
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.


METHODS
We have evaluated 31 primary ovarian cancers and matched normal DNA for loss of heterozygosity and copy number alterations using 500 K 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.
Gorringe
Kylie L
KL
Victorian Breast Cancer Research Consortium Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
Jacobs
Sharoni
S
Thompson
Ella R
ER
Sridhar
Anita
A
Qiu
Wen
W
Choong
David Y H
DY
Campbell
Ian G
IG
D022981:Allelic Imbalance; D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D048670:MAP Kinase Kinase 4; C482559:MAP2K4 protein, human