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A notable exception is colorectal cancer, in which loss of function of p16 and RB and amplification of cyclin D genes are rarely observed. A distinct spectrum of oncogenes and tumor suppressor genes are targets of genetic alteration in colonic epithelium. These include APC in the majority of cases, as well as involvement of a group of genes that regulate DNA mismatch repair in nonpolypoid cancers [B. Vogelstein and K. W. Kinzler, Cold Spring Harbor Symp. Quant. Biol. 59, 517 (1994); R. Kolodner, Genes Dev. 10, 1433 (1996)]. Colonic epithelium may be unusual because of its extremely high rate of self-renewal. Given that mutation of a gene can abrogate the selective pressure for inactivating other genes in the same pathway, a provocative possibility is that the APC gene product regulates p16. Alternatively, defects in the RB pathway may induce genomic instability, which, in colon cancer, would instead be a consequence of faulty mismatch repair.
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(1994)
Cold Spring Harbor Symp. Quant. Biol.
, vol.59
, pp. 517
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Vogelstein, B.1
Kinzler, K.W.2
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196
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0029784320
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A notable exception is colorectal cancer, in which loss of function of p16 and RB and amplification of cyclin D genes are rarely observed. A distinct spectrum of oncogenes and tumor suppressor genes are targets of genetic alteration in colonic epithelium. These include APC in the majority of cases, as well as involvement of a group of genes that regulate DNA mismatch repair in nonpolypoid cancers [B. Vogelstein and K. W. Kinzler, Cold Spring Harbor Symp. Quant. Biol. 59, 517 (1994); R. Kolodner, Genes Dev. 10, 1433 (1996)]. Colonic epithelium may be unusual because of its extremely high rate of self-renewal. Given that mutation of a gene can abrogate the selective pressure for inactivating other genes in the same pathway, a provocative possibility is that the APC gene product regulates p16. Alternatively, defects in the RB pathway may induce genomic instability, which, in colon cancer, would instead be a consequence of faulty mismatch repair.
-
(1996)
Genes Dev.
, vol.10
, pp. 1433
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Kolodner, R.1
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198
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10544254542
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note
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I thank S, Baker, R. Bram, T. Curran, S. d'Azzo, J. Downing, S. Elledge, G. Grosveld, S. Hiebert, J. Ihle, T. Jacks, A. T. Look, J. Roberts, M. Roussel, D. Shapiro, and the members of my laboratory for discussions and helpful comments about the manuscript. C.J.S. is an investigator of the Howard Hughes Medical Institute.
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