Kong X T, Choi S H, Inoue A, Takita J, Yokota J, Hanada R, Yamamoto K, Bessho F, Yanagisawa M, Hayashi Y
Department of Paediatrics, University of Tokyo, Japan.
Eur J Cancer. 1997 Oct;33(12):1962-5. doi: 10.1016/s0959-8049(97)00209-8.
The deleted in colorectal carcinoma (DCC) gene, a candidate tumour suppressor, might be inactivated in a number of human cancers. In order to evaluate the possible role of DCC alterations in the pathogenesis of neuroblastoma, we examined 25 neuroblastoma cell lines and 16 primary tumours, including 6 samples with loss of heterozygosity (LOH) at the DCC locus for DCC mRNA expression, by using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. The level of DCC expression was significantly reduced or undetectable in 12 of 25 (48%) cell lines and 7 of 16 (44%) primary tumours, suggesting that inactivation of the DCC gene is involved in the development of neuroblastoma. Three of the 6 tumours with LOH at the DCC locus revealed reduced DCC mRNA expression, indicating that LOH at the DCC locus might have affected the levels of DCC mRNA. We also screened for mutations in 4 exons of the DCC gene in 12 cell lines by using PCR-single strand conformation polymorphism (PCR-SSCP) analysis. Point mutations were not found except a polymorphic change at codon 201. The mechanism for inactivation of the DCC gene will be further investigated.
结直肠癌缺失基因（DCC）是一种候选肿瘤抑制基因，可能在多种人类癌症中失活。为了评估DCC改变在神经母细胞瘤发病机制中的可能作用，我们采用逆转录聚合酶链反应（RT-PCR）技术，检测了25个神经母细胞瘤细胞系和16个原发性肿瘤，包括6个在DCC基因座存在杂合性缺失（LOH）的样本，以检测DCC mRNA表达情况。在25个细胞系中的12个（48%）和16个原发性肿瘤中的7个（44%）中，DCC表达水平显著降低或无法检测到，这表明DCC基因失活与神经母细胞瘤的发生发展有关。在DCC基因座存在LOH的6个肿瘤中，有3个显示DCC mRNA表达降低，这表明DCC基因座的LOH可能影响了DCC mRNA的水平。我们还通过PCR-单链构象多态性（PCR-SSCP）分析，对12个细胞系中DCC基因的4个外显子进行了突变筛查。除了密码子201处的一个多态性改变外，未发现点突变。DCC基因失活的机制将进一步研究。
