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APC mutations occur early during colorectal tumorigenesis

Abstract

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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References

  1. Fearon, E. R. & Vogelstein, B. Cell 61, 759–767 (1990).

    Article  CAS  Google Scholar 

  2. Weinberg, R. A. Science 254, 1138–1146 (1991).

    Article  ADS  CAS  Google Scholar 

  3. Bishop, J. M. Cell 64, 235–248 (1991).

    Article  CAS  Google Scholar 

  4. Kinzler, K. W. et al. Science 253, 661–665 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Joslyn, G. et al. Cell 66, 601–613 (1991).

    Article  CAS  Google Scholar 

  6. Nishisho, I. et al. Science 253, 665–669 (1991).

    Article  ADS  CAS  Google Scholar 

  7. Groden, J. et al. Cell 66, 589–600 (1991).

    Article  CAS  Google Scholar 

  8. Miyoshi, Y. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4452–4456 (1992).

    Article  ADS  CAS  Google Scholar 

  9. Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C. C. Science 253, 49–53 (1991).

    Article  ADS  CAS  Google Scholar 

  10. Rideout, W. M., Coetzee, G. A., Olumi, A. F. & Jones, P. A. Science 249, 1288–1290 (1990).

    Article  ADS  CAS  Google Scholar 

  11. Vogelstein, B. et al. New Eng. J. Med. 319, 525–532 (1988).

    Article  CAS  Google Scholar 

  12. Cannon-Albright, L. A., Skolnick, M. H., Bishop, T., Lee, R. G. & Burt, R. W. New Engl. J. Med. 319, 533–537 (1988).

    Article  CAS  Google Scholar 

  13. Baker, S. J. et al. Cancer Res. 50, 7717–7722 (1990).

    CAS  PubMed  Google Scholar 

  14. Waddell, W. R., Ganser, G. F., Cerise, E. J. & Loughry, R. W. Am. J. Surg. 156, 175–179 (1989).

    Article  Google Scholar 

  15. Su, L.-K. et al. Science 256, 668–670 (1992).

    Article  ADS  CAS  Google Scholar 

  16. Sidransky, D. et al. Science 256, 102–105 (1992).

    Article  ADS  CAS  Google Scholar 

  17. Turnbull, R. B., Kyle, K., Watson, F. R. & Spratt, J. Ann. Surg. 166, 420–427 (1967).

    Article  Google Scholar 

  18. Spirio, L., Joslyn, G., Nelson, L., Leppert, M. & White, R. Nucleic Acids Res. 19, 6348 (1991).

    Article  CAS  Google Scholar 

  19. Wijnen, J. et al. Nucleic Acids Res. 19, 6965 (1991).

    Article  CAS  Google Scholar 

  20. Kinzler, K. W. et al. Science 251, 1366–1370 (1991).

    Article  ADS  CAS  Google Scholar 

  21. Boynton, R. F. et al. Proc. natn. Acad. Sci. U.S.A. 89, 3385–3388 (1992).

    Article  ADS  CAS  Google Scholar 

  22. Nigro, J. M. et al. Nature 342, 705–708 (1989).

    Article  ADS  CAS  Google Scholar 

Download references

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Powell, S., Zilz, N., Beazer-Barclay, Y. et al. APC mutations occur early during colorectal tumorigenesis. Nature 359, 235–237 (1992). https://doi.org/10.1038/359235a0

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