Chromosomes 6 and 18 induce neoplastic suppression in epithelial ovarian cancer cells

Metaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13,14,15 and 18 are frequently deleted in primary ovarian cancers (OCs). Therefore we used microcell-mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes into 2 epithelial OC cell lines l TO VT12D arid TOV21G). The in vitro neoplastic phenotype (measured as anchorage dependent and independent growth and invasion) was compared between recipient OC cell lines and multiple MMCT hybrids. Chromosomes 6 and 18 showed strong evidence of functional, neoplastic suppression for multiple hybrids in both cell lines. We also found evidence in 1 cancer cell line suggesting that chromosomes 4, 13 and 14 may also cause functional suppression. Array CCH and microsatellite analyses were used to characterise the extent of genomic transfer in chromosome 6 and 18 hybrids. .4 36 MB deletion on chromosome 6 in 2 hybrids from 1 cell line mapped the candidate region proximal to 6ql5 and distal to 6q22.2; and an ∼10 MB candidate region spanning the centromere on chromosome 18 was identified in 2 hybrids from the other cell line. These data support reported functional effects of chromosome 6 in OC cell lines; but to our knowledge, this is the first time that functional suppression for chromosome 18 has been reported. This suggests that these chromosomes may harbour tumour suppres-sor-"like" genes. The future identification of these genes may have a signiicant impact on the understanding and treatment of the disease and the identileation of novel therapeutic targets.