Goh H S, Yao J, Smith D R
Department of Colorectal Surgery, Singapore General Hospital, Republic of Singapore.
Cancer Res. 1995 Nov 15;55(22):5217-21.
We have examined the relationship between point mutation of the p53 tumor suppressor gene and survival in colorectal cancer patients. We found that patients with tumors harboring mutated p53 genes showed a significantly poorer prognosis than did those patients with genes without point mutations, and, moreover, patient response to postoperative therapies depended significantly on mutation status in both adjuvant and palliative treatment cohorts. However, not all point mutations were the same functionally; point mutations within the conserved domains of the p53 tumor suppressor gene were inherently more aggressive than tumors with point mutations outside of these domains, and mutations of codon 175 were particularly aggressive. These results suggest that knowledge of a patient's p53 status, both with respect to the presence of point mutations and to the specific nature of the lesion, may be required to accurately predict both the course of the disease and the response of the disease to postoperative therapeutic interventions, especially those therapies based on the induction of apoptosis in the neoplastic cell.
我们研究了p53肿瘤抑制基因的点突变与结直肠癌患者生存率之间的关系。我们发现，携带p53基因突变的肿瘤患者的预后明显比那些基因无点突变的患者差，此外，患者对术后治疗的反应在辅助治疗和姑息治疗队列中均显著取决于突变状态。然而，并非所有的点突变在功能上都是相同的；p53肿瘤抑制基因保守结构域内的点突变本质上比这些结构域外有突变的肿瘤更具侵袭性，且密码子175的突变尤其具有侵袭性。这些结果表明，可能需要了解患者的p53状态，包括点突变的存在情况以及病变的具体性质，才能准确预测疾病的进程以及疾病对术后治疗干预的反应，尤其是那些基于诱导肿瘤细胞凋亡的治疗方法。
