Praml C, Amler L C, Dihlmann S, Finke L H, Schlag P, Schwab M
Department of Cytogenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Oncogene. 1998 Oct 15;17(15):2009-12. doi: 10.1038/sj.onc.1202121.
There is good evidence now that the secretory type II phospholipase A2 (Pla2g2a) gene represents the Mom1 locus, a genetic modifier of tumor resistance in the multiple intestinal neoplasia (Min) mouse. Previously we have mapped the human homolog PLA2G2A to 1p35-36.1 within a region that is the target of frequent deletions in sporadic colorectal tumors. Here we show 64% loss of heterozygosity (LOH) at the PLA2G2A locus in primary tumors. We studied PLA2G2A expression in both colorectal tumor cell lines and normal mucosa. Most of the lines lacked detectable PLA2G2A transcripts by Northern analysis. Large differences in expression were seen among normal mucosa of different patients with sporadic tumors. We analysed the coding region of PLA2G2A in eight colorectal cancer cell lines with hemizygous deletion at 1p35-36/PLA2G2A, in none we did detect a mutation. Biallelic expression of PLA2G2A was observed in a cell line heterozygous for an exon 3 polymorphism, rendering unlikely that imprinting is a pathway participating in the loss of PLA2G2A function. It remains uncertain if PLA2G2A, in particular its apparent lack of expression in tumor cells, might be a factor in human colorectal tumorigenesis.
目前有充分证据表明,分泌型II型磷脂酶A2(Pla2g2a)基因代表Mom1位点,它是多肠肿瘤(Min)小鼠肿瘤抗性的遗传修饰因子。此前我们已将人类同源基因PLA2G2A定位到1p35 - 36.1,该区域是散发性结直肠癌肿瘤中频繁缺失的靶点。在此我们发现原发性肿瘤中PLA2G2A位点杂合性缺失(LOH)率为64%。我们研究了PLA2G2A在结直肠肿瘤细胞系和正常黏膜中的表达情况。通过Northern分析,大多数细胞系未检测到可检测的PLA2G2A转录本。在散发性肿瘤不同患者的正常黏膜中观察到表达存在很大差异。我们分析了8个在1p35 - 36/PLA2G2A处存在半合子缺失的结直肠癌细胞系中PLA2G2A的编码区,未检测到任何突变。在一个外显子3多态性杂合的细胞系中观察到PLA2G2A的双等位基因表达,这使得印记不太可能是参与PLA2G2A功能丧失的途径。PLA2G2A,特别是其在肿瘤细胞中明显缺乏表达,是否可能是人类结直肠癌发生的一个因素仍不确定。