Shen Xing-jun, Ali-Fehmi Rouba, Weng Chang-Ren, Sarkar Fazlul H, Grignon David, Liao D Joshua
Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan 48201, USA.
Cancer Biol Ther. 2006 May;5(5):523-8. doi: 10.4161/cbt.5.5.2610. Epub 2006 May 15.
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.
QM基因位于X染色体的Xq28区域。QM可能作为一种肿瘤抑制因子，也可能参与60S核糖体亚基的组装。我们研究了29例卵巢癌活检组织中Xq28区域微卫星标记DXS15A、DXS1107、WI12360和WI9327的杂合性缺失（LOH）和微卫星不稳定性（MSI）。结果显示，WI12360、WI9327、DXS1107和DXS15A的LOH频率分别为18.2%、30%、26.3%和20.8%，而MSI率分别为18.2%、50.0%、31.6%和12.5%。所有肿瘤至少对这些标记中的一个显示出LOH或MSI。对QM cDNA进行测序，除了第605个核苷酸处的腺嘌呤（A）/鸟嘌呤（G）替换（该替换使编码从丝氨酸变为天冬酰胺）外，未发现任何其他突变。在29个肿瘤中的17个（58.6%）中，检测到了A和G两种类型的QM mRNA，表明QM是A/G杂合的且逃避了X染色体失活。然而，cDNA和基因组DNA测序显示，在17例中的3例中，相邻正常组织显示出A/G杂合性，而在其余14例中，4例没有更多相邻组织可供检测，10例在第605个核苷酸处显示为G或A，表明这些肿瘤中存在A/G点突变。A和G型QM基因的等位基因分布分别为32.8%和67.2%。在癌组织中，A/A、G/G和A/G纯合或杂合的频率分别为3.5%、37.9%和58.6%，但在相邻组织中分别为26.1%、52.2%和21.7%，表明癌组织中的杂合率更高（58.6%对21.7%，p<0.01）。这些结果表明，Xq28处的高频率LOH和MSI以及QM基因第605个核苷酸处的A/G杂合性可能与卵巢癌有关。
