Loss of expression of the DRR I gene at chromosomal segment 3p21.1 in Renal cell carcinoma

Liang Wang, John Darling, Jin San Zhang, Wanguo Liu, Junqi Qian, David Bostwick, Lynn Hartmann, Robert Brian Jenkins, Walter Bardenhauer, Jochen Schutte, Bertram Opalka, David I Smith

Research output: Contribution to journalArticle

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Abstract

Consistent deletion of DNA sequences in chromosomal band 3p21 observed in a variety of human tumors suggests the presence of one or more tumor suppressor genes within this region. Previously, we reported on the construction of two distinct cosmid contigs and our identification of several new genes within 3p21.1. In our search for tumor suppressor genes from this region, we have cloned a gene that we have called DRR I (downregulated in renal cell carcinoma). The gene was first mapped to 3p21.1 by fluorescence in situ hybridization analysis. Further analysis of yeast artificial chromosome clones in 3p14.2-p21.1 refined its localization. DRR I spans about 10 Kb of genomic DNA with a 3.5-Kb mature transcript. The putative protein encoded by this gene is 144 amino acids and includes a nuclear localization signal and a coiled domain. The gene showed loss of expression in eight of eight renal cell carcinoma cell lines, one of seven ovarian cancer cell lines, one of one cervical cancer cell line, one of one gastric cancer cell line, and one of one non-small-cell lung cancer cell line. Southern blot analysis did not show any altered bands, indicating that gross structural changes or deletions did not cause the loss of expression. This gene was also found to have reduced expression in 23 of 34 paired primary renal cell carcinomas. Mutational analysis detected three polymorphic sites within the gene, but no point mutations were identified in the 34 primary tumors. However, we did detect base substitutions in 4 of 12 cell lines that had undetectable expression of the gene. We also transfected the gene into DRR I-negative cell lines and observed clear growth retardation. Our results suggest that loss of expression of the DRR I gene may play an important role in the development of renal cell carcinoma and possibly other tumors.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalGenes Chromosomes and Cancer
Volume27
Issue number1
DOIs
StatePublished - Jan 2000

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Renal Cell Carcinoma
Cell Line
Genes
Tumor Suppressor Genes
Yeast Artificial Chromosomes
Nuclear Localization Signals
Neoplasms
Cosmids
Southern Blotting
Fluorescence In Situ Hybridization
Point Mutation
Non-Small Cell Lung Carcinoma
Uterine Cervical Neoplasms
Ovarian Neoplasms
Stomach Neoplasms
Down-Regulation
Clone Cells
Gene Expression
Amino Acids
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Loss of expression of the DRR I gene at chromosomal segment 3p21.1 in Renal cell carcinoma. / Wang, Liang; Darling, John; Zhang, Jin San; Liu, Wanguo; Qian, Junqi; Bostwick, David; Hartmann, Lynn; Jenkins, Robert Brian; Bardenhauer, Walter; Schutte, Jochen; Opalka, Bertram; Smith, David I.

In: Genes Chromosomes and Cancer, Vol. 27, No. 1, 01.2000, p. 1-10.

Research output: Contribution to journalArticle

Wang, L, Darling, J, Zhang, JS, Liu, W, Qian, J, Bostwick, D, Hartmann, L, Jenkins, RB, Bardenhauer, W, Schutte, J, Opalka, B & Smith, DI 2000, 'Loss of expression of the DRR I gene at chromosomal segment 3p21.1 in Renal cell carcinoma', Genes Chromosomes and Cancer, vol. 27, no. 1, pp. 1-10. https://doi.org/10.1002/(SICI)1098-2264(200001)27:1<1::AID-GCC1>3.0.CO;2-6
Wang, Liang ; Darling, John ; Zhang, Jin San ; Liu, Wanguo ; Qian, Junqi ; Bostwick, David ; Hartmann, Lynn ; Jenkins, Robert Brian ; Bardenhauer, Walter ; Schutte, Jochen ; Opalka, Bertram ; Smith, David I. / Loss of expression of the DRR I gene at chromosomal segment 3p21.1 in Renal cell carcinoma. In: Genes Chromosomes and Cancer. 2000 ; Vol. 27, No. 1. pp. 1-10.
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AU - Bostwick, David

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AU - Jenkins, Robert Brian

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