Allelic loss of a common microsatellite marker MYCL1:: A useful prognostic factor of poor outcomes in colorectal cancer
Allelic loss of a common microsatellite marker MYCL1:: A useful prognostic factor of poor outcomes in colorectal cancer
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DOI：
10.1158/1078-0432.ccr-0779-3
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发表时间：
2004-03-01
影响因子：
11.5
通讯作者：
Matsubara, N
中科院分区：
文献类型：
--
作者：
Kambara, T;Sharp, GB;Matsubara, N
目的：涉及染色体臂5q、8p、17p和18q的等位基因缺失在结直肠癌（CRC）中很常见。1号染色体的短臂也经常在包括CRC在内的一系列癌症类型中受到影响。我们在本研究中的目的是确定1p上的等位基因缺失是否可能在预测CRC病例的预后方面具有很大价值。实验设计：从90例CRC根治性切除患者的肿瘤及相应的正常组织标本中制备基因组DNA。使用14个微卫星标记检测染色体臂1p、2p、5q、7q、8p、17p、17q和18q上的杂合性缺失（LOH），并探讨LOH与临床病理因素（包括肿瘤复发和患者生存）之间的可能相关性。74例MYCL1微卫星标记1p34处的LOH在12例（16.2%）患者中检测到该标记。结果：在控制肿瘤分期和性别并排除远处转移患者的发现后，我们发现MYCL1 LOH阳性患者复发的可能性是该位点LOH阴性患者的31倍（95%置信区间为2.27-无穷大；P = 0.04）。在1p35的14-3-3-sigma-TG微卫星标记处有类似的LOH倾向，但我们没有发现该部位LOH与肿瘤复发或患者生存之间有显著关联的证据。我们也无法检测到2p、5q、7q、8p、17p、17q和18q上不同位点的LOH与肿瘤复发或患者生存之间的显著关联。结论：肿瘤在1p34染色体MYCL1位点出现LOH的结直肠癌患者预后可能较差，提示该标志物可能具有临床相关性。
Purpose: Allelic loss involving chromosome arms 5q, 8p, 17p, and 18q is commonly detected in colorectal cancer (CRC). The short arm of chromosome 1 is also frequently affected in a whole range of cancer types, including CRC. Our aim in the present study was to determine whether allelic losses on 1p were likely to be of much value in predicting the prognosis of CRC cases.Experimental Design: Genomic DNA was prepared from tumor and corresponding normal tissue specimens from 90 patients who had undergone curative resection for CRC. Loss of heterozygosity (LOH) on chromosome arms 1p, 2p, 5q, 7q, 8p, 17p, 17q, and 18q was examined using 14 microsatellite markers, and possible correlations between LOH and clinicopathological factors (including tumor recurrence and patient survival) were investigated. LOH at the MYCL1 microsatellite marker at 1p34 was detected in 12 of 74 (16.2%) patients who were informative for this marker.Results: After controlling for tumor stage and gender and excluding findings for patients with remote metastasis, we found that patients who were positive for LOH at MYCL1 were 31 times more likely to experience recurrence than those who were negative for LOH at this locus (95% confidence intervals, 2.27-infinity; P = 0.04). There were indications of a similar tendency for LOH at the 14-3-3-sigma-TG microsatellite marker at 1p35, but we could find no evidence of a significant association between LOH at this site and tumor recurrence or patient survival. We were also unable to detect significant association between LOH at the various sites on 2p, 5q, 7q, 8p, 17p, 17q, and 18q and either tumor recurrence or patient survival.Conclusions: CRC patients whose tumors exhibited LOH at MYCL1 at chromosome 1p34 were likely to have a poor prognosis, suggesting that this marker may have clinical relevance.