APC MUTATIONS OCCUR EARLY DURING COLORECTAL TUMORIGENESIS
APC MUTATIONS OCCUR EARLY DURING COLORECTAL TUMORIGENESIS
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DOI：
10.1038/359235a0
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发表时间：
1992-09-17
期刊：
影响因子：
64.8
通讯作者：
KINZLER, KW
中科院分区：
文献类型：
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作者：
POWELL, SM;ZILZ, N;KINZLER, KW
人类肿瘤发生与癌基因和肿瘤抑制基因突变的积累有关1 -3。但是，在普通的成人癌症中，还没有发现在致瘤过程的早期阶段起关键作用的突变。我们试图确定APC基因的突变是否在人类结直肠肿瘤中发挥这种作用，这种肿瘤在几十年的时间里从小的良性肿瘤（腺瘤）演变为较大的恶性肿瘤（癌）。在这里，我们报告的序列分析41结直肠肿瘤显示，大多数结直肠癌（60%）和腺瘤（63%）含有突变的APC基因。此外，APC基因符合肿瘤起始的两个重要标准。首先，在可以分析的最早期肿瘤中发现了该基因的突变，包括直径小至0.5厘米的腺瘤。其次，随着肿瘤从良性发展到恶性，这种突变的频率保持不变。这些数据提供了强有力的证据，APC基因的突变在结直肠肿瘤的早期发展中发挥了重要作用。
HUMAN tumorigenesis is associated with the accumulation of mutations both in oncogenes and in tumour suppressor genes1-3. But in no common adult cancer have the mutations that are critical in the early stages of the tumorigenic process been defined. We have attempted to determine if mutations of the APC gene play such a role in human colorectal tumours, which evolve from small benign tumours (adenomas) to larger malignant tumours (carcinomas) over the course of several decades. Here we report that sequence analysis of 41 colorectal tumours revealed that the majority of colorectal carcinomas (60%) and adenomas (63%) contained a mutated APC gene. Furthermore, the APC gene met two criteria of importance for tumour initiation. First, mutations of this gene were found in the earliest tumours that could be analysed, including adenomas as small as 0.5 cm in diameter. Second, the frequency of such mutations remained constant as tumours progressed from benign to malignant stages. These data provide strong evidence that mutations of the APC gene play a major role in the early development of colorectal neoplasms.