Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Mar;84(6):743–747. doi: 10.1054/bjoc.2000.1667

Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma

W Fang 1, Z Piao 1, I M Buyse 1,1, D Simon 2, J C Sheu 3, M Perucho 1, S Huang 1
PMCID: PMC2363805  PMID: 11259086

Abstract

The RIZ (PRDM2) locus commonly undergoes loss of heterozygosity (LOH) and maps within the minimal deleted region on 1p36 in hepatocellular carcinoma (HCC). Although peptide-altering mutations of RIZ are rare in HCC, the RIZ1 product is commonly lost in HCC and has tumour suppressive activities. Here, we analysed RIZ gene mutations and LOH in HCC, breast cancer, familial melanoma, colon cancer, and stomach cancer. We found 7 polymorphisms but no mutations. By analysing the Pro704-deletion polymorphism, we detected LOH of RIZ in 31 of 79 (39%) informative HCC cases, 11 of 47 (23%) colon cancer cases, 8 of 43 (19%) breast cancer cases, 8 of 66 (12%) stomach cancer cases. Importantly, loss of the Pro704+allele was found in 74% of the 31 LOH positive HCC cases (P< 0.01), indicating a preferential loss and hence a stronger tumour suppressor role for this allele compared to the P704allele. In addition, the Pro704+allele was found to be more common in Asians (0.61) than Caucasians (0.42) (P = 0.0000), suggesting an interesting link between gene polymorphisms and potential differences in tumour incidence between racial groups. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: RIZ (PRDM2), polymorphisms, hepatoma

Full Text

The Full Text of this article is available as a PDF (80.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbondanza C., Medici N., Nigro V., Rossi V., Gallo L., Piluso G., Belsito A., Roscigno A., Bontempo P., Puca A. A. The retinoblastoma-interacting zinc-finger protein RIZ is a downstream effector of estrogen action. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3130–3135. doi: 10.1073/pnas.050015697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bale S. J., Dracopoli N. C., Tucker M. A., Clark W. H., Jr, Fraser M. C., Stanger B. Z., Green P., Donis-Keller H., Housman D. E., Greene M. H. Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p. N Engl J Med. 1989 May 25;320(21):1367–1372. doi: 10.1056/NEJM198905253202102. [DOI] [PubMed] [Google Scholar]
  3. Bardi G., Pandis N., Fenger C., Kronborg O., Bomme L., Heim S. Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis. Cancer Res. 1993 Apr 15;53(8):1895–1898. [PubMed] [Google Scholar]
  4. Baylin S. B., Herman J. G. DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet. 2000 Apr;16(4):168–174. doi: 10.1016/s0168-9525(99)01971-x. [DOI] [PubMed] [Google Scholar]
  5. Buyse I. M., Shao G., Huang S. The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4467–4471. doi: 10.1073/pnas.92.10.4467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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. Candidate tumor suppressor RIZ is frequently involved in colorectal carcinogenesis. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2662–2667. doi: 10.1073/pnas.040579497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eng C., Herman J. G., Baylin S. B. A bird's eye view of global methylation. Nat Genet. 2000 Feb;24(2):101–102. doi: 10.1038/72730. [DOI] [PubMed] [Google Scholar]
  8. Fang W., Piao Z., Simon D., Sheu J. C., Huang S. Mapping of a minimal deleted region in human hepatocellular carcinoma to 1p36.13-p36.23 and mutational analysis of the RIZ (PRDM2) gene localized to the region. Genes Chromosomes Cancer. 2000 Jul;28(3):269–275. [PubMed] [Google Scholar]
  9. Genuardi M., Tsihira H., Anderson D. E., Saunders G. F. Distal deletion of chromosome Ip in ductal carcinoma of the breast. Am J Hum Genet. 1989 Jul;45(1):73–82. [PMC free article] [PubMed] [Google Scholar]
  10. Hammond C., Jeffers L., Carr B. I., Simon D. Multiple genetic alterations, 4q28, a new suppressor region, and potential gender differences in human hepatocellular carcinoma. Hepatology. 1999 May;29(5):1479–1485. doi: 10.1002/hep.510290513. [DOI] [PubMed] [Google Scholar]
  11. He L., Yu J. X., Liu L., Buyse I. M., Wang M. S., Yang Q. C., Nakagawara A., Brodeur G. M., Shi Y. E., Huang S. RIZ1, but not the alternative RIZ2 product of the same gene, is underexpressed in breast cancer, and forced RIZ1 expression causes G2-M cell cycle arrest and/or apoptosis. Cancer Res. 1998 Oct 1;58(19):4238–4244. [PubMed] [Google Scholar]
  12. Huang S., Shao G., Liu L. The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J Biol Chem. 1998 Jun 26;273(26):15933–15939. doi: 10.1074/jbc.273.26.15933. [DOI] [PubMed] [Google Scholar]
  13. Jiang G. l., Liu L., Buyse I. M., Simon D., Huang S. Decreased RIZ1 expression but not RIZ2 in hepatoma and suppression of hepatoma tumorigenicity by RIZ1. Int J Cancer. 1999 Nov 12;83(4):541–546. doi: 10.1002/(sici)1097-0215(19991112)83:4<541::aid-ijc17>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  14. Jones P. A., Laird P. W. Cancer epigenetics comes of age. Nat Genet. 1999 Feb;21(2):163–167. doi: 10.1038/5947. [DOI] [PubMed] [Google Scholar]
  15. Kuroki T., Fujiwara Y., Tsuchiya E., Nakamori S., Imaoka S., Kanematsu T., Nakamura Y. Accumulation of genetic changes during development and progression of hepatocellular carcinoma: loss of heterozygosity of chromosome arm 1p occurs at an early stage of hepatocarcinogenesis. Genes Chromosomes Cancer. 1995 Jul;13(3):163–167. doi: 10.1002/gcc.2870130305. [DOI] [PubMed] [Google Scholar]
  16. Landis S. H., Murray T., Bolden S., Wingo P. A. Cancer statistics, 1999. CA Cancer J Clin. 1999 Jan-Feb;49(1):8-31, 1. doi: 10.3322/canjclin.49.1.8. [DOI] [PubMed] [Google Scholar]
  17. Lin Y. W., Sheu J. C., Huang G. T., Lee H. S., Chen C. H., Wang J. T., Lee P. H., Lu F. J. Chromosomal abnormality in hepatocellular carcinoma by comparative genomic hybridisation in Taiwan. Eur J Cancer. 1999 Apr;35(4):652–658. doi: 10.1016/s0959-8049(98)00430-4. [DOI] [PubMed] [Google Scholar]
  18. Liu L., Shao G., Steele-Perkins G., Huang S. The retinoblastoma interacting zinc finger gene RIZ produces a PR domain-lacking product through an internal promoter. J Biol Chem. 1997 Jan 31;272(5):2984–2991. doi: 10.1074/jbc.272.5.2984. [DOI] [PubMed] [Google Scholar]
  19. Muraosa Y., Takahashi K., Yoshizawa M., Shibahara S. cDNA cloning of a novel protein containing two zinc-finger domains that may function as a transcription factor for the human heme-oxygenase-1 gene. Eur J Biochem. 1996 Feb 1;235(3):471–479. doi: 10.1111/j.1432-1033.1996.00471.x. [DOI] [PubMed] [Google Scholar]
  20. Piao Z., Fang W., Malkhosyan S., Kim H., Horii A., Perucho M., Huang S. Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability. Cancer Res. 2000 Sep 1;60(17):4701–4704. [PubMed] [Google Scholar]
  21. Piao Z., Park C., Park J. H., Kim H. Allelotype analysis of hepatocellular carcinoma. Int J Cancer. 1998 Jan 5;75(1):29–33. doi: 10.1002/(sici)1097-0215(19980105)75:1<29::aid-ijc5>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  22. Piao Z., Park C., Park J. H., Kim H. Deletion mapping of chromosome 4q in hepatocellular carcinoma. Int J Cancer. 1998 Aug 21;79(4):356–360. doi: 10.1002/(sici)1097-0215(19980821)79:4<356::aid-ijc8>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  23. Rea S., Eisenhaber F., O'Carroll D., Strahl B. D., Sun Z. W., Schmid M., Opravil S., Mechtler K., Ponting C. P., Allis C. D. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000 Aug 10;406(6796):593–599. doi: 10.1038/35020506. [DOI] [PubMed] [Google Scholar]
  24. Sakurada K., Furukawa T., Kato Y., Kayama T., Huang S., Horii A. RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum. Genes Chromosomes Cancer. 2001 Feb;30(2):207–211. [PubMed] [Google Scholar]
  25. Shapiro V. S., Lee P., Winoto A. Identification and cloning of the G3B cDNA encoding a 3' segment of a protein binding to GATA-3. Gene. 1995 Oct 3;163(2):329–330. doi: 10.1016/0378-1119(95)00420-b. [DOI] [PubMed] [Google Scholar]
  26. Simon D., Knowles B. B., Weith A. Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas. Oncogene. 1991 May;6(5):765–770. [PubMed] [Google Scholar]
  27. Weith A., Brodeur G. M., Bruns G. A., Matise T. C., Mischke D., Nizetic D., Seldin M. F., van Roy N., Vance J. Report of the second international workshop on human chromosome 1 mapping 1995. Cytogenet Cell Genet. 1996;72(2-3):114–144. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES