Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G heterozygosity of the QM gene are associated with ovarian cancer.
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Shen XJ, Ali-Fehmi R, Weng CR, Sarkar FH, Grignon D, Liao DJ
Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G heterozygosity of the QM gene are associated with ovarian cancer.
Cancer Biol Ther. 2006 May;5(5):523-8. Epub 2006 May 15.
- PubMed ID
- 16627977 [ View in PubMed]
- Abstract
The QM gene is located at Xq28 of the X chromosome. QM may act as a tumor suppressor and may also participate in the 60S ribosomal subunit assembly. We studied loss of heterozygosity (LOH) and microsatellite instability (MSI) of microsatellite markers DXS15A, DXS1107, WI12360 and WI9327 for the Xq28 region in 29 ovarian cancer biopsies. The results showed that the LOH frequencies were 18.2%, 30%, 26.3% and 20.8% for WI12360, WI9327, DXS1107 and DXS15A, respectively, whereas the MSI rates were 18.2%, 50.0%, 31.6% and 12.5%, respectively. All tumors showed LOH or MSI for at least one of these markers. Sequencing the QM cDNA did not identify any mutation other than the adenine (A)/guanine (G) replacement at the 605th nucleotide which changes the coding from serine to asparagine. In 17 (58.6%) of the 29 tumors, both A and G types of QM mRNA were detected, indicating that the QM was A/G heterozygous and escaped X-inactivation. However, cDNA and genomic DNA sequencing revealed that the adjacent normal tissues showed the A/G heterozygosity in only 3 of the 17 cases, while in the remaining 14 cases, four had no more adjacent tissue available and ten revealed either G or A at the 605th nt, indicating an A/G point mutation in these tumors. The allele distribution was 32.8% for the A and 67.2% for the G type QM gene. The frequencies of A/A, G/G and A/G homo- or hetero-zygosity were 3.5%, 37.9% and 58.6%, respectively in cancer tissues but they were 26.1%, 52.2% and 21.7%, respectively in the adjacent tissues, indicating a higher heterozygous rate in cancer (58.6% vs 21.7%, p < 0.01). These results suggest that high frequencies of LOH and MSI at the Xq28 and of the A/G heterozygosity at the 605th nt of the QM gene may be associated with ovarian cancer.