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Science 14 April 1989:
Vol. 244. no. 4901, pp. 217 - 221
DOI: 10.1126/science.2649981
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Articles

Science, Vol 244, Issue 4901, 217-221
Copyright © 1989 by American Association for the Advancement of Science

articles

Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas

SJ Baker, ER Fearon, JM Nigro, Hamilton SR, AC Preisinger, JM Jessup, P vanTuinen, DH Ledbetter, DF Barker, Y Nakamura, R White, and B Vogelstein

Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used to localize the common region of deletion in these tumors to a region contained within bands 17p12 to 17p13.3. This region contains the gene for the transformation-associated protein p53. Southern and Northern blot hybridization experiments provided no evidence for gross alterations of the p53 gene or surrounding sequences. As a more rigorous test of the possibility that p53 was a target of the deletions, the p53 coding regions from two tumors were analyzed; these two tumors, like most colorectal carcinomas, had allelic deletions of chromosome 17p and expressed considerable amounts of p53 messenger RNA from the remaining allele. The remaining p53 allele was mutated in both tumors, with an alanine substituted for valine at codon 143 of one tumor and a histidine substituted for arginine at codon 175 of the second tumor. Both mutations occurred in a highly conserved region of the p53 gene that was previously found to be mutated in murine p53 oncogenes. The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 gene.


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Mutations of the p53 Gene as a Prognostic Factor in Aggressive B-Cell Lymphoma.
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p53 and Breast Cancer.
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Accelerated neuronal differentiation induced by p53 suppression.
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Chromosome 17p Allelic Loss in Colorectal Carcinoma: Clinical Significance.
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A p53-dependent mouse spindle checkpoint.
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Science 267, 1353-1356
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Cloning of Tumor Suppressor Genes Involved in Solid Tumor Development.
D. I. Smith and M. del Mar Alonso (1993)
Arch Otolaryngol Head Neck Surg 119, 1210-1216
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Human Cytogenetics: A Current Overview.
M. M. Cohen, L. S. Rosenblum-Vos, and G. Prabhakar (1993)
Arch Pediatr Adolesc Med 147, 1159-1166
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Clinical Implications of the p53 Tumor-Suppressor Gene.
C. C. Harris and M. Hollstein (1993)
N. Engl. J. Med. 329, 1318-1327
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S. Thibodeau, G Bren, and D Schaid (1993)
Science 260, 816-819
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Determination of Tumor Aggressiveness in Colorectal Cancer by K-ras-2 Analysis.
S. D. Finkelstein, R. Sayegh, A. Bakker, and P. Swalsky (1993)
Arch Surg 128, 526-532
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Science 260, 85-88
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Reconciling the Epidemiology, Physiology, and Molecular Biology of Colon Cancer.
J. D. Potter (1992)
JAMA 268, 1573-1577
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Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element..
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S. Kern, J. Pietenpol, S Thiagalingam, A Seymour, K. Kinzler, and B Vogelstein (1992)
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DCC: A Tumor Suppressor Gene Expressed on the Cell Surface.
L. Hedrick, K.R. Cho, J. Boyd, J. Risinger, and B. Vogelstein (1992)
Cold Spring Harb Symp Quant Biol 57, 345-351
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p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts..
D M Harvey and A J Levine (1991)
Genes & Dev. 5, 2375-2385
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Tumor suppressor genes.
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Science 254, 1153-1160
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Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.
I Nishisho, Y Nakamura, Y Miyoshi, Y Miki, H Ando, A Horii, K Koyama, J Utsunomiya, S Baba, and P Hedge (1991)
Science 253, 665-669
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p53 mutations in human cancers.
M Hollstein, D Sidransky, B Vogelstein, and C. Harris (1991)
Science 253, 49-53
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Identification of p53 as a sequence-specific DNA-binding protein.
S. Kern, K. Kinzler, A Bruskin, D Jarosz, P Friedman, C Prives, and B Vogelstein (1991)
Science 252, 1708-1711
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Identification of p53 gene mutations in bladder cancers and urine samples.
D Sidransky, A Von Eschenbach, Y. Tsai, P Jones, I Summerhayes, F Marshall, M Paul, P Green, Hamilton SR, P Frost, et al. (1991)
Science 252, 706-709
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Ubiquitin Hybrid Protein Gene Expression During Human Colon Cancer Progression.
K.-i. Mafune, J. M. Wong, R. J. Staniunas, M. L. Lu, T. S. Ravikumar, L. B. Chen, and G. D. Steele Jr (1991)
Arch Surg 126, 462-466
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Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers.
K. Kinzler, M. Nilbert, B Vogelstein, T. Bryan, D. Levy, K. Smith, A. Preisinger, Hamilton SR, P Hedge, A Markham, et al. (1991)
Science 251, 1366-1370
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Science 251, 796-799
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Cold Spring Harb Symp Quant Biol 56, 219-225
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Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.
D Malkin, F. Li, L. Strong, J. Fraumeni Jr, C. Nelson, D. Kim, J Kassel, M. Gryka, F. Bischoff, M. Tainsky, et al. (1990)
Science 250, 1233-1238
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Different tumor-derived p53 mutants exhibit distinct biological activities.
O Halevy, D Michalovitz, and M Oren (1990)
Science 250, 113-116
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Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene.
L Raycroft, H. Wu, and G Lozano (1990)
Science 249, 1049-1051
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Suppression of human colorectal carcinoma cell growth by wild-type p53.
S. Baker, S Markowitz, E. Fearon, J. Willson, and B Vogelstein (1990)
Science 249, 912-915
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Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients.
M. Wallace, D. Marchuk, L. Andersen, R Letcher, H. Odeh, A. Saulino, J. Fountain, A Brereton, J Nicholson, A. Mitchell, et al. (1990)
Science 249, 181-186
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Association of human papillomavirus types 16 and 18 E6 proteins with p53.
B. Werness, A. Levine, and P. Howley (1990)
Science 248, 76-79
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SV40 stimulates expression of the transacting factor Sp1 at the mRNA level..
J D Saffer, S P Jackson, and S J Thurston (1990)
Genes & Dev. 4, 659-666
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L. A. Liotta and E. Kohn (1990)
JAMA 263, 1123-1126
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Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6.
J. Trent, E. Stanbridge, H. McBride, E. Meese, G Casey, D. Araujo, C. Witkowski, and R. Nagle (1990)
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Genes & Dev. 4, 1-8
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Tumor suppressor genes: the puzzle and the promise.
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Science 246, 1406-1412
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G1 events and regulation of cell proliferation.
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Science 246, 603-608
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Science 246, 491-494
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