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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >The 18q21 region in colorectal and pancreatic cancer: independent loss of DCC and DPC4 expression
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The 18q21 region in colorectal and pancreatic cancer: independent loss of DCC and DPC4 expression

机译：大肠癌和胰腺癌的18q21区：DCC和DPC4表达的独立丧失

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The 18q21 region is frequently altered in gastrointestinal tumors. Three candidate tumor suppressor genes have been identified in it: DCC, Smad4|DPC4 and Smad2; the mechanisms involving their inactivation have not been completely elucidated. In this study, genetic losses at 18q21 and expression of DCC and DPC4 in colorectal (n = 12) and pancreatic (n = 16) cell lines and in colorectal tissues (n = 10) were analyzed. The status of the 18q21 region was assessed using microsatellite analysis and duplex PCR of exonic sequences; expression was analyzed by RT-PCR; mutational analysis of DPC4 cDNA was performed in selected cases. Homozygous losses of microsatellite markers at 18q21 were not observed in colon or pancreas lines; however, a higher proportion of apparent homozygosity than expected was found. DCC and DPC4 transcripts were detected in 11/12 and 12/12 colorectal cancer lines, respectively. In tumors, homozygous losses at 18q21 were detected in three cases, without affecting DCC. All tumors retained DCC and DPC4 mRNA expression. In pancreatic lines, DPC4 was inactivated through homozygous deletion (n = 5), intragenic mutation (n = 3), and lack of protein (n = 2). In conclusion: (1) microsatellite analysis does not provide adequate information regarding homozygous losses at 18q21; (2) approximately 65% of pancreas cancer lines show inactivation of DPC4; and (3) loss of DCC and DPC4 occur independently.
机译：18q21区在胃肠道肿瘤中经常发生变化。其中已经鉴定出三个候选的抑癌基因：DCC，Smad4 | DPC4和Smad2;和尚未完全阐明涉及其失活的机制。在这项研究中，分析了18q21时的遗传损失以及大肠（n = 12）和胰腺（n = 16）细胞系以及大肠组织（n = 10）中DCC和DPC4的表达。使用微卫星分析和外显子序列的双重PCR评估18q21区的状态;通过RT-PCR分析表达;在选定的病例中进行了DPC4 cDNA的突变分析。在结肠或胰腺品系中未观察到18q21时微卫星标记的纯合丢失。但是，表观纯合子的比例比预期的高。在11/12和12/12大肠癌细胞系中分别检测到DCC和DPC4转录本。在肿瘤中，在三例中检测到18q21处的纯合子丢失，而没有影响DCC。所有肿瘤均保留DCC和DPC4 mRNA表达。在胰腺细胞系中，DPC4通过纯合缺失（n = 5），基因内突变（n = 3）和蛋白质缺乏（n = 2）而失活。结论：（1）微卫星分析没有提供有关18q21纯合损失的足够信息; （2）约65％的胰腺癌系显示DPC4失活; （3）DCC和DPC4的丢失是独立发生的。

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