Kambara Takeshi, Sharp Gerald B, Nagasaka Takeshi, Takeda Masanori, Sasamoto Hiromi, Nakagawa Hitoshi, Isozaki Hiroshi, MacPhee Donald G, Jass Jeremy R, Tanaka Noriaki, Matsubara Nagahide
Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Clin Cancer Res. 2004 Mar 1;10(5):1758-63. doi: 10.1158/1078-0432.ccr-0779-3.
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.
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.
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.
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.
在结直肠癌(CRC)中常检测到涉及染色体臂5q、8p、17p和18q的等位基因缺失。1号染色体短臂在包括CRC在内的多种癌症类型中也经常受到影响。我们在本研究中的目的是确定1p上的等位基因缺失在预测CRC病例预后方面是否可能具有重要价值。
从90例接受了CRC根治性切除的患者的肿瘤及相应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),并研究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。在74例该标记信息有效的患者中,有12例(16.2%)检测到1p34处MYCL1微卫星标记的LOH。
在控制肿瘤分期和性别并排除远处转移患者的结果后,我们发现MYCL1处LOH阳性的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,2.27 - 无穷大;P = 0.04)。在1p35处的14 - 3 - 3 - sigma - TG微卫星标记处的LOH有类似的趋势,但我们没有发现该位点的LOH与肿瘤复发或患者生存之间存在显著关联的证据。我们也未能检测到2p、5q、7q、8p、17p、17q和18q上各位点的LOH与肿瘤复发或患者生存之间的显著关联。
肿瘤在1号染色体p34处的MYCL1显示出LOH的CRC患者可能预后不良,这表明该标记可能具有临床相关性。