DOI: 10.1073/pnas.040579497. Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis

Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis

10.1073/pnas.040579497

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The distal portion of chromosome 1p is one of the most commonly affected regions in human cancer. In this study of hereditary and sporadic colorectal cancer, a region of frequent deletion was identified at 32.2 centimorgans from 1ptel. Deletion breakpoints clustered in the vicinity of or inside the gene RIZ , which encodes a retinoblastoma protein-interacting zinc finger protein. Sequence analysis revealed frequent frameshift mutations of the RIZ gene. The mutations consisted of 1- or 2-bp deletions of a coding (A) 8 or (A) 9 tract and were confined to microsatellite-unstable colorectal tumors, being present in 9 of 24 (37.5%) primary tumors and in 6 of 11 (54.5%) cell lines; in 2 cell lines the mutation was homozygous/hemizygous. The mutations apparently were selected clonally in tumorigenesis, because similar poly(A) tracts in other genes were not affected. Two alternative products of the gene exist, RIZ1, which contains a PR ( P RDI-BF1- R IZ1) domain implicated in tumor suppressor function, and RIZ2, which is lacking this motif. Furthermore, the C-terminal region, which contains the poly(A) tracts, includes a PR-binding motif, possibly mediating interactions with other proteins or with RIZ itself (oligomerization). Four of eleven microsatellite-unstable colorectal cancer cell lines, three of which had frameshifts, showed reduced or absent mRNA expression of RIZ1. In a cell line that is homozygous/hemizygous for the typical frameshift mutation, immunoblotting showed truncated RIZ protein, whereas adenovirus-mediated RIZ1 expression caused G 2 /M arrest and apoptosis. We propose that RIZ is a target of the observed 1p alterations, with impairment of the PR domain-mediated function through either frameshift mutation or genomic deletion.

Bibliography

Chadwick, R. B., Jiang, G.-L., Bennington, G. A., Yuan, B., Johnson, C. K., Stevens, M. W., Niemann, T. H., Peltomaki, P., Huang, S., & de la Chapelle, A. (2000). Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis. Proceedings of the National Academy of Sciences, 97(6), 2662â2667.

Authors 10

Robert B. Chadwick (first)
Guang-Liang Jiang (additional)
Garth A. Bennington (additional)
Bo Yuan (additional)
Cheryl K. Johnson (additional)
Michael W. Stevens (additional)
Theodore H. Niemann (additional)
Paivi Peltomaki (additional)
Shi Huang (additional)
Albert de la Chapelle (additional)

References 22 Referenced 121

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L He, J X Yu, L Liu, I M Buyse, M-S Wang, Q-C Yang, A Nakagawara, G M Brodeur, Y E Shi, S Huang Cancer Res 58, 4238–4244 (1998). / Cancer Res by He L (1998)
10.1002/(SICI)1097-0215(19991112)83:4<541::AID-IJC17>3.0.CO;2-F
G-L Jiang, S Huang Histol Histopathol 15, 109–117 (2000). / Histol Histopathol by Jiang G-L (2000)
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C R Boland, S N Thibodeau, S R Hamilton, D Sidransky, J R Eshleman, R W Burt, S J Meltzer, M A Rodriguez-Bigas, R Fodde, G N Ranzani, S Srivastava Cancer Res 58, 5248–5257 (1998). / Cancer Res by Boland C R (1998)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:41 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:31 a.m.)
Indexed	3 weeks, 6 days ago (July 30, 2025, 10:57 a.m.)
Issued	25 years, 6 months ago (Feb. 25, 2000)
Published	25 years, 6 months ago (Feb. 25, 2000)
Published Online	25 years, 6 months ago (Feb. 25, 2000)
Published Print	25 years, 5 months ago (March 14, 2000)

Funders 0

None

BibTeX

@article{Chadwick_2000, title={Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.040579497}, DOI={10.1073/pnas.040579497}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chadwick, Robert B. and Jiang, Guang-Liang and Bennington, Garth A. and Yuan, Bo and Johnson, Cheryl K. and Stevens, Michael W. and Niemann, Theodore H. and Peltomaki, Paivi and Huang, Shi and de la Chapelle, Albert}, year={2000}, month=feb, pages={2662–2667} }

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  "abstract": "<jats:p>\n            The distal portion of chromosome 1p is one of the most commonly\n affected regions in human cancer. In this study of hereditary and\n sporadic colorectal cancer, a region of frequent deletion was\n identified at 32.2 centimorgans from 1ptel. Deletion breakpoints\n clustered in the vicinity of or inside the gene\n            <jats:italic>RIZ</jats:italic>\n            ,\n which encodes a retinoblastoma protein-interacting zinc finger protein.\n Sequence analysis revealed frequent frameshift mutations of the\n            <jats:italic>RIZ</jats:italic>\n            gene. The mutations consisted of 1- or 2-bp\n deletions of a coding (A)\n            <jats:sub>8</jats:sub>\n            or (A)\n            <jats:sub>9</jats:sub>\n            tract and\n were confined to microsatellite-unstable colorectal tumors, being\n present in 9 of 24 (37.5%) primary tumors and in 6 of 11 (54.5%) cell\n lines; in 2 cell lines the mutation was homozygous/hemizygous. The\n mutations apparently were selected clonally in tumorigenesis, because\n similar poly(A) tracts in other genes were not affected. Two\n alternative products of the gene exist, RIZ1, which contains a PR\n (\n            <jats:underline>P</jats:underline>\n            RDI-BF1-\n            <jats:underline>R</jats:underline>\n            IZ1) domain implicated in tumor\n suppressor function, and RIZ2, which is lacking this motif.\n Furthermore, the C-terminal region, which contains the poly(A) tracts,\n includes a PR-binding motif, possibly mediating interactions with other\n proteins or with RIZ itself (oligomerization). Four of eleven\n microsatellite-unstable colorectal cancer cell lines, three of which\n had frameshifts, showed reduced or absent mRNA expression of RIZ1. In a\n cell line that is homozygous/hemizygous for the typical frameshift\n mutation, immunoblotting showed truncated RIZ protein, whereas\n adenovirus-mediated RIZ1 expression caused G\n            <jats:sub>2</jats:sub>\n            /M arrest\n and apoptosis. We propose that RIZ is a target of the observed\n 1p alterations, with impairment of the PR domain-mediated function\n through either frameshift mutation or genomic deletion.\n          </jats:p>",
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