Ichimiya S, Nimura Y, Kageyama H, Takada N, Sunahara M, Shishikura T, Nakamura Y, Sakiyama S, Seki N, Ohira M, Kaneko Y, McKeon F, Caput D, Nakagawara A
Division of Biochemistry, Chiba Cancer Center Research Institute, Japan.
Med Pediatr Oncol. 2001 Jan;36(1):42-4. doi: 10.1002/1096-911X(20010101)36:1<42::AID-MPO1011>3.0.CO;2-K.
Human p73, a novel homolog of p53, has recently been cloned and mapped at chromosome 1p36.3, the locus for putative tumor suppressor gene(s) of neuroblastoma (NBL) and other cancers. p73, like p53, inhibits growth and induces apoptosis in neuroblastoma and osteosarcoma cell lines.
To test the hypothesis that p73 is a NBL suppressor gene, we examined expression, allelo-typing, and mutation of the p73 gene in primary human neuroblastomas. Loss of heterozygosity (LOH) for p73 was performed in 272 primary NBLs using a CT repeat polymorphic marker, which we found in intron 9 of the p73 gene.
p73 LOH was observed in 28 out of 151 (19%) informative cases. The high frequency of p73 LOH was significantly associated with sporadic neuroblastomas (P< 0.001), MYCN amplification (P< 0.001), and advanced stages (P< 0.05). Mutational analyses by PCR-SSCP (single strand conformation polymorphism) revealed two mis-sense mutations in 140 NBLs, one somatic and one germline.
Thus, the present results have shown that mutation of p73 is infrequent in NBLs, although the p73 locus is frequently lost in advanced stage tumors. These suggest that p73 may not be a tumor suppressor in the classic Knudson manner.
人p73是p53的一种新型同源物，最近已被克隆并定位在1p36.3染色体上，该位点是神经母细胞瘤（NBL）和其他癌症假定肿瘤抑制基因的所在位置。与p53一样，p73在神经母细胞瘤和骨肉瘤细胞系中抑制生长并诱导凋亡。
为了验证p73是一种NBL抑制基因的假设，我们检测了原发性人类神经母细胞瘤中p73基因的表达、等位基因分型和突变情况。使用我们在p73基因内含子9中发现的一个CT重复多态性标记，对272例原发性NBL进行了p73杂合性缺失（LOH）检测。
在151例信息充分的病例中，有28例（19%）观察到p73 LOH。p73 LOH的高频率与散发性神经母细胞瘤（P<0.001）、MYCN扩增（P<0.001）和晚期（P<0.05）显著相关。通过PCR-SSCP（单链构象多态性）进行的突变分析在140例NBL中发现了两个错义突变，一个是体细胞突变，一个是种系突变。
因此，目前的结果表明，尽管p73位点在晚期肿瘤中经常丢失，但p73在NBL中的突变并不常见。这些结果提示p73可能不是经典的Knudson方式的肿瘤抑制基因。
