Abstract
The distal short arm of chromosome 1 is commonly deleted in a variety of human neoplasms including gastrointestinal cancer. Genetic alterations of the retinoblastoma protein-interacting zing-finger gene (RIZ)1 including loss of heterozygosity (LOH) at 1p36, frameshift mutations, and promoter hypermethylation were reported previously in several cancers. In this study, we evaluated RIZ1 in 30 primary gastric cancers and found frameshift mutations in two cases (6.7%). Moreover, using real-time quantitative methylation-specific PCR, methylation of the RIZ1 promoter was detected in 11 (37%) cases. In all 11 cases with methylation, inactivation of the second allele occurred through frameshift mutation, LOH or promoter methylation. Our results suggest that RIZ1 is a specific target of inactivation in human gastric cancer.
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References
Buyse IM, Shao G and Huang S . (1995). Proc. Natl. Acad. Sci. USA, 92, 4467–4471.
Chadwick RB, Jiang GL, Bennington GA, Yuan B, Johnson CK, Stevens MW, Niemann TH, Peltomaki P, Huang S and de la Chapelle A . (2000). Proc. Natl. Acad. Sci. USA, 97, 2662–2667.
Du Y, Carling T, Fang W, Piao Z, Sheu JC and Huang S . (2001). Cancer Res., 61, 8094–8099.
Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV and Laird PW . (2000). Nucleic Acids Res., 28, E32.
Esteller M, Corn PG, Baylin SB and Herman JG . (2001). Cancer Res., 61, 3225–3229.
Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB and Herman JG . (2000). Cancer Res., 60, 4366–4371.
Fang W, Piao Z, Simon D, Sheu JC and Huang S . (2000). Genes Chromosomes Cancer, 28, 269–275.
Jiang G, Liu L, Buyse IM, Simon D and Huang S . (1999). Int. J. Cancer, 83, 541–546.
Jones PA and Laird PW . (1999). Nat. Genet., 21, 163–167.
Nawroz H, Koch W, Anker P, Stroun M and Sidransky D . (1996). Nat. Med., 2, 1035–1037.
Nomoto S, Haruki N, Tatematsu Y, Konishi H, Mitsudomi T and Takahashi T . (2000). Genes Chromosomes Cancer, 28, 342–346.
Piao Z, Fang W, Malkhosyan S, Kim H, Horii A, Perucho M and Huang S . (2000). Cancer Res., 60, 4701–4704.
Sakurada K, Furukawa T, Kato Y, Kayama T, Huang S and Horii A . (2001). Genes Chromosomes Cancer, 30, 207–211.
Schwab M, Praml C and Amler LC . (1996). Genes Chromosomes Cancer, 16, 211–229.
Sobin LH and Wittekind Ch. (ed) (1997). TNM Classification of Malignant Tumours. Wiley-Liss: New York.
Steele-Perkins G, Fang W, Yang XH, Van Gele M, Carling T, Gu J, Buyse IM, Fletcher JA, Liu J, Bronson R, Chadwick RB, de la Chapelle A, Zhang X, Speleman F and Huang S . (2001). Genes Dev., 15, 2250–2262.
Toyota M, Ahuja N, Suzuki H, Itoh F, Ohe-Toyota M, Imai K, Baylin SB and Issa JP . (1999). Cancer Res., 59, 5438–5442.
Tsuchiya T, Tamura G, Sato K, Endoh Y, Sakata K, Jin Z, Motoyama T, Usuba O, Kimura W, Nishizuka S, Wilson KT, James SP, Yin J, Fleisher AS, Zou T, Silverberg SG, Kong D and Meltzer SJ . (2000). Oncogene, 19, 3642–3646.
Usadel H, Brabender J, Danenberg KD, Jeronimo C, Harden S, Engles J, Danenberg PV, Yang S and Sidransky D . (2002). Cancer Res., 62, 371–375.
Weith A, Brodeur GM, Bruns GA, Matise TC, Mischke D, Nizetic D, Seldin MF, van Roy N and Vance J . (1996). Cytogenet Cell Genet., 72, 114–144.
Acknowledgements
We thank Dr Loio Santos for the enrollment of patients in this study. This paper is supported by the NCI/EDRN Grant (1 U01 CA84986) entitled, ‘Integrated Development of Novel Molecular Markers – The Early Detection Research Network.’
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Tokumaru, Y., Nomoto, S., Jerónimo, C. et al. Biallelic inactivation of the RIZ1 gene in human gastric cancer. Oncogene 22, 6954–6958 (2003). https://doi.org/10.1038/sj.onc.1206403
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DOI: https://doi.org/10.1038/sj.onc.1206403
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