Gokgoz N, Wunder J S, Mousses S, Eskandarian S, Bell R S, Andrulis I L
Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Cancer. 2001 Oct 15;92(8):2181-9. doi: 10.1002/1097-0142(20011015)92:8<2181::aid-cncr1561>3.0.co;2-3.
In some malignancies, p53 mutations are associated with tumor progression. To address the role of p53 mutations in the development and progression of osteosarcoma, the authors analyzed specimens from 247 patients with primary localized osteosarcomas and 25 patients with osteosarcomas that were metastatic at the time of diagnosis. The group included 27 matched biopsy-resection specimens and 21 biopsy-metastasis paired specimens.
The authors examined the nature and location of p53 mutations (exons 4-10) by polymerase chain reaction-single-strand conformation polymorphism and confirmed mutations by direct DNA sequencing.
The overall frequency of p53 mutations was 22% (60 of 272 specimens), with 13 of 60 mutations located in exons 4 or 10. A similar proportion of localized osteosarcomas had alterations of the p53 gene (55 of 247 specimens; 22.3%) compared with tumors from patients who had metastases at the time of diagnosis (5 of 25 specimens; 20%; P = 0.96). Patients who had p53 missense mutations were older compared with patients who had nonsense alterations or a wild type gene (P = 0.01). Examination of paired biopsy-resection and biopsy-metastasis specimens revealed that the p53 status was concordant between the biopsy and later tumor specimens in all patients.
The p53 mutation status did not differentiate between patients who presented with a localized osteosarcoma and those who presented with metastases at the time of diagnosis. The current data indicate that p53 mutations are not late events in osteosarcoma tumor progression, because they are evident before the development of metastases. The inclusion of exons 4 and 10 increased the sensitivity of the analysis.
在某些恶性肿瘤中，p53突变与肿瘤进展相关。为了探讨p53突变在骨肉瘤发生发展及进展中的作用，作者分析了247例原发性局限性骨肉瘤患者以及25例诊断时已发生转移的骨肉瘤患者的标本。该组包括27对匹配的活检 - 切除标本以及21对活检 - 转移配对标本。
作者通过聚合酶链反应 - 单链构象多态性检测p53突变（外显子4 - 10）的性质和位置，并通过直接DNA测序确认突变。
p53突变的总体频率为22%（272个标本中的60个），60个突变中有13个位于外显子4或10。与诊断时已有转移的患者的肿瘤相比，局限性骨肉瘤中p53基因改变的比例相似（247个标本中的55个；22.3%）（25个标本中的5个；20%；P = 0.96）。与有无义改变或野生型基因的患者相比，有p53错义突变的患者年龄更大（P = 0.01）。对配对的活检 - 切除标本和活检 - 转移标本的检查显示，所有患者的活检标本和后来的肿瘤标本之间p53状态一致。
p53突变状态在诊断时表现为局限性骨肉瘤的患者和已有转移的患者之间并无差异。目前的数据表明，p53突变不是骨肉瘤肿瘤进展中的晚期事件，因为它们在转移发生之前就已明显。纳入外显子4和10提高了分析的敏感性。
