Loss of Heterozygosity of the Nm23-H1 Gene in Human Renal Cell Carcinomas

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 1997 Jan 1

PMID 9341897

Citations 4

Authors

M H Bosnar

K Pavelic

R Hrascan

Z Zeljko

I Krhen

Z Marekoyic

S Krizanac

J Pavelic

Affiliations

Soon will be listed here.

Abstract

This study evaluates the potential contribution of the nm23-H1 gene to malignant transformation in patients with renal cell carcinoma. Using specific oligonucleotide primers for the nm23-H1 microsatellite repetitive sequence, gene instability was followed by polymerase chain reaction/loss of heterozygosity assay on 54 tumor specimens and the corresponding normal tissue samples. We also determined, immunohistochemically, the relative concentration and localization of the nm23-H1 protein product. From 77.7% informative cases, DNA from 6 tumors exhibited loss of heterozygosity, regardless of the tumor stage (TNM). Out of 39 samples analyzed, 30 were negative for Nm23-H1 protein, while the others were only slightly positive. No correlation with tumor stage was found. Normal renal tissue was also negative for this protein. Our results provide the evidence for loss of heterozygosity, followed by means of microsatellite tandem-repeat polymorphism, at the nm23-H1 locus in renal cell carcinoma. However, since no correlation was found between the tumor stage or metastatic potential on the one hand, and allelic loss and specific protein expression on the other, it seems that nm23-H1 does not play a key role in the invasiveness of this tumor type.

Citing Articles

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nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma.

Kapitanovic S, Cacev T, Berkovic M, Popovic-Hadzija M, Radosevic S, Seiwerth S J Clin Pathol. 2004; 57(12):1312-8.

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Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

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Nm23/nucleoside diphosphate kinase in human cancers.

Hartsough M, Steeg P J Bioenerg Biomembr. 2002; 32(3):301-8.

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References

Strohmeyer T, Slamon D . Proto-oncogenes and tumor suppressor genes in human urological malignancies. J Urol. 1994; 151(6):1479-97. DOI: 10.1016/s0022-5347(17)35284-9. View

Jeffreys A, Wilson V, Thein S . Hypervariable 'minisatellite' regions in human DNA. Nature. 1985; 314(6006):67-73. DOI: 10.1038/314067a0. View

Higashiyama M, Doi O, Yokouchi H, Kodama K, Nakamori S, Tateishi R . Immunohistochemical analysis of nm23 gene product/NDP kinase expression in pulmonary adenocarcinoma: lack of prognostic value. Br J Cancer. 1992; 66(3):533-6. PMC: 1977950. DOI: 10.1038/bjc.1992.308. View

Florenes V, Aamdal S, Myklebost O, Maelandsmo G, Bruland O, Fodstad O . Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res. 1992; 52(21):6088-91. View

Pavelic J, Galltroselj K, Hlavka V, Pavelic Z, Gluckman J, Stambrook P . Nm23-h1 protein in oligodendrogliomas. Int J Oncol. 2011; 4(6):1399-403. DOI: 10.3892/ijo.4.6.1399. View

Hiasa Y, Konishi N, Tao M, Matsuda H, Tsumatani K, Nakamura Y . Different expression of nm23-H1 and nm23-H2 protein with proliferative activities in various sizes of human renal cell carcinoma. Oncology. 1996; 53(1):79-87. DOI: 10.1159/000227540. View

Pavelic K, Pavelic Z, Preisler H . c-myc detection in bone marrow biopsies. Leuk Res. 1991; 15(11):1075-8. DOI: 10.1016/0145-2126(91)90114-9. View

Yamakawa K, Morita R, Takahashi E, Hori T, Ishikawa J, Nakamura Y . A detailed deletion mapping of the short arm of chromosome 3 in sporadic renal cell carcinoma. Cancer Res. 1991; 51(17):4707-11. View

Leone A, MCBRIDE O, Weston A, Wang M, Anglard P, Cropp C . Somatic allelic deletion of nm23 in human cancer. Cancer Res. 1991; 51(9):2490-3. View

10.

Walther M, Anglard P, Gnarra J, Pozzatti R, Venzon D, De la Rosa A . Expression of nm23 in cell lines derived from patients with metastatic renal cell carcinoma. J Urol. 1995; 154(1):278-82. View

11.

Greenberg R, Howard S, Bruzel A, Bremer M, Goll A, Salazar H . Comprehensive allelotyping of human renal cell carcinomas using microsatellite DNA probes. Proc Natl Acad Sci U S A. 1995; 92(7):2854-8. PMC: 42317. DOI: 10.1073/pnas.92.7.2854. View

12.

Steeg P, Bevilacqua G, Kopper L, Thorgeirsson U, Talmadge J, Liotta L . Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988; 80(3):200-4. DOI: 10.1093/jnci/80.3.200. View

13.

Uchida T, Wada C, Wang C, Egawa S, Ohtani H, Koshiba K . Genomic instability of microsatellite repeats and mutations of H-, K-, and N-ras, and p53 genes in renal cell carcinoma. Cancer Res. 1994; 54(14):3682-5. View

14.

Wang L, Patel U, Ghosh L, Chen H, Banerjee S . Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res. 1993; 53(4):717-20. View

15.

Ishikawa J, Xu H, Hu S, Yandell D, Maeda S, Kamidono S . Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas. Cancer Res. 1991; 51(20):5736-43. View

16.

Hughson M, Meloni A, Dougherty S, Silva F, Sandberg A . Analysis of 3p allelic loss in papillary and nonpapillary renal cell carcinomas. Correlation with tumor karyotypes. Cancer Genet Cytogenet. 1996; 87(2):133-9. DOI: 10.1016/0165-4608(95)00274-x. View

17.

Pavelic K, Pavelic Z, Denton D, Reising J, Khalily M, Preisler H . Immunohistochemical detection of c-myc oncoprotein in paraffin embedded tissues. J Exp Pathol. 1990; 5(4):143-53. View

18.

Haut M, Steeg P, WILLSON J, Markowitz S . Induction of nm23 gene expression in human colonic neoplasms and equal expression in colon tumors of high and low metastatic potential. J Natl Cancer Inst. 1991; 83(10):712-6. DOI: 10.1093/jnci/83.10.712. View

19.

Bugert P, Kovacs G . Molecular differential diagnosis of renal cell carcinomas by microsatellite analysis. Am J Pathol. 1996; 149(6):2081-8. PMC: 1865333. View