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Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer

Oncogene volume 23, pages 6612–6620 (2004)Cite this article

Abstract

Loss of heterozygosity (LOH) studies indicate that genetic alterations of chromosome 9p occur in numerous tumor types, suggesting the presence of tumor suppressor genes (TSGs) on chromosome 9p critical in carcinogenesis. Our previous LOH analyses in primary lung tumors led us to propose that chromosome 9p harbors other TSGs important in lung tumorigenesis. In this study, 30 non-small-cell lung cancer and 12 small-cell lung cancer cell lines were screened with 55 markers to identify new regions of homozygous deletion (HD) on chromosome 9p. Three novel noncontiguous homozygously deleted regions were detected and ranged in size from 840 kb to 7.4 Mb. One gene identified in the deletion at D9S126, TUSC1 (tumor suppressor candidate 1), is an intronless gene. Multiplex polymerase chain reaction and Southern blot confirmed the HD of TUSC1. Northern blot analysis of TUSC1 demonstrated two transcripts of approximately 2 and 1.5 kb that are likely generated by alternative polyadenylation signals. Both transcripts are expressed in several human tissues and share an open-reading frame encoding a peptide of 209 amino acids. Analysing cell line cDNAs by reverse transcriptase (RT)–PCR demonstrated downregulation of TUSC1 in cell lines with or without HDs, suggesting that TUSC1 may play a role in lung tumorigenesis.

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Acknowledgements

We would like to thank both Dr Curtis C Harris (Laboratory of Human Carcinogenesis, NCI) and the Developmental Therapeutics Program (NCI) for providing several lung cancer cell lines, Dr Douglas Lowy (Laboratory of Cellular Oncology, NCI) and CCR Fellow Editorial Board (NCI) for critical comments on the manuscript.

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  1. Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Bethesda, 20892-4258, MD, USA

    Zhihong Shan, Tracy Parker & Jonathan S Wiest

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  1. Zhihong Shan
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  2. Tracy Parker
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Correspondence to Jonathan S Wiest.

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Sequence data from this article have been deposited into the GenBank under Accession number: AY168647, AY546089

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Shan, Z., Parker, T. & Wiest, J. Identifying novel homozygous deletions by microsatellite analysis and characterization of tumor suppressor candidate 1 gene, TUSC1, on chromosome 9p in human lung cancer. Oncogene 23, 6612–6620 (2004). https://doi.org/10.1038/sj.onc.1207857

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