TY - JOUR
T1 - APC mutations occur early during colorectal tumorigenesis
AU - Powell, Steven M.
AU - Zilz, Nathan
AU - Beazer-Barclay, Yasmin
AU - Bryan, Tracy M.
AU - Hamilton, Stanley R.
AU - Thibodeau, Stephen N.
AU - Vogelstein, Bert
AU - Kinzler, Kenneth W.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
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U2 - 10.1038/359235a0
DO - 10.1038/359235a0
M3 - Article
C2 - 1528264
AN - SCOPUS:0026630266
SN - 0028-0836
VL - 359
SP - 235
EP - 237
JO - Nature
JF - Nature
IS - 6392
ER -