The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma

Kunbo Zhang, Norbert Dion, Bruno Fuchs, Tim Damron, Steven Gitelis, Ronald Irwin, Mary O'Connor, Herbert Schwartz, Sean P. Scully, Michael G. Rock, Mark E. Bolander, Gobinda Sarkar

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The hSEP1 gene is the human homolog of yeast SEP1. Yeast SEP1 is a multifunctional gene that regulates a variety of nuclear and cytoplasmic functions including homologous recombination, meiosis, telomere maintenance, RNA metabolism and microtubule assembly. The function of hSEP1 is not known. We show loss or reduced expression of hSEP1 messenger RNA (mRNA) in three of four primary osteogenic sarcoma (OGS)-derived cell lines and in eight of nine OGS biopsy specimen. In addition, we find a heterozygous missence mutation (Valine 1484>Alanine) at a conserved amino acid in the primary OGS-derived cell line U2OS. Importantly, we identified a homozygous missense mutation involving a CG-dinucleotide leading to a change in a conserved amino acid, aspartic acid 1137 >asparagine, in the primary OGS-derived cell line, TE85. hSEP1 mRNA expression was nearly undetectable in TE85 and low in U2OS cell lines. None of these mutations were identified in 20 normal samples consisting of bone, cartilage and fibroblast. The hSEP1 gene is located in chromosome 3 at 3q25-26.1 between markers D3S1309 and D3S1569. An adjacent locus defined by the polymorphic markers D3S1212 and D3S1245 has previously been reported to undergo loss of heterozygosity (LOH) at a >70% frequency in OGS and claimed to harbor an important tumor suppressor gene in osteosarcoma. The homozygous mutation in the hSEP1 mRNA in TE85 cell line suggest that this gene itself is subject to LOH. Taken together, these results suggest that hSEP1 acts as a tumor suppressor gene in OGS.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalGene
Volume298
Issue number2
DOIs
StatePublished - Oct 20 2002

Fingerprint

Osteosarcoma
Tumor Suppressor Genes
Yeasts
Cell Line
Loss of Heterozygosity
Messenger RNA
Mutation
Genes
Amino Acids
Chromosomes, Human, Pair 3
Asparagine
Homologous Recombination
Telomere
Meiosis
Valine
Missense Mutation
Aspartic Acid
Microtubules
Alanine
Cartilage

Keywords

  • Biopsy
  • Human homolog of yeast sep1
  • Loss of heterozygosity
  • Mutation
  • Osteogenic sarcoma
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Genetics

Cite this

Zhang, K., Dion, N., Fuchs, B., Damron, T., Gitelis, S., Irwin, R., ... Sarkar, G. (2002). The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma. Gene, 298(2), 121-127. https://doi.org/10.1016/S0378-1119(02)00929-0

The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma. / Zhang, Kunbo; Dion, Norbert; Fuchs, Bruno; Damron, Tim; Gitelis, Steven; Irwin, Ronald; O'Connor, Mary; Schwartz, Herbert; Scully, Sean P.; Rock, Michael G.; Bolander, Mark E.; Sarkar, Gobinda.

In: Gene, Vol. 298, No. 2, 20.10.2002, p. 121-127.

Research output: Contribution to journalArticle

Zhang, K, Dion, N, Fuchs, B, Damron, T, Gitelis, S, Irwin, R, O'Connor, M, Schwartz, H, Scully, SP, Rock, MG, Bolander, ME & Sarkar, G 2002, 'The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma', Gene, vol. 298, no. 2, pp. 121-127. https://doi.org/10.1016/S0378-1119(02)00929-0
Zhang, Kunbo ; Dion, Norbert ; Fuchs, Bruno ; Damron, Tim ; Gitelis, Steven ; Irwin, Ronald ; O'Connor, Mary ; Schwartz, Herbert ; Scully, Sean P. ; Rock, Michael G. ; Bolander, Mark E. ; Sarkar, Gobinda. / The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma. In: Gene. 2002 ; Vol. 298, No. 2. pp. 121-127.
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abstract = "The hSEP1 gene is the human homolog of yeast SEP1. Yeast SEP1 is a multifunctional gene that regulates a variety of nuclear and cytoplasmic functions including homologous recombination, meiosis, telomere maintenance, RNA metabolism and microtubule assembly. The function of hSEP1 is not known. We show loss or reduced expression of hSEP1 messenger RNA (mRNA) in three of four primary osteogenic sarcoma (OGS)-derived cell lines and in eight of nine OGS biopsy specimen. In addition, we find a heterozygous missence mutation (Valine 1484>Alanine) at a conserved amino acid in the primary OGS-derived cell line U2OS. Importantly, we identified a homozygous missense mutation involving a CG-dinucleotide leading to a change in a conserved amino acid, aspartic acid 1137 >asparagine, in the primary OGS-derived cell line, TE85. hSEP1 mRNA expression was nearly undetectable in TE85 and low in U2OS cell lines. None of these mutations were identified in 20 normal samples consisting of bone, cartilage and fibroblast. The hSEP1 gene is located in chromosome 3 at 3q25-26.1 between markers D3S1309 and D3S1569. An adjacent locus defined by the polymorphic markers D3S1212 and D3S1245 has previously been reported to undergo loss of heterozygosity (LOH) at a >70{\%} frequency in OGS and claimed to harbor an important tumor suppressor gene in osteosarcoma. The homozygous mutation in the hSEP1 mRNA in TE85 cell line suggest that this gene itself is subject to LOH. Taken together, these results suggest that hSEP1 acts as a tumor suppressor gene in OGS.",
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author = "Kunbo Zhang and Norbert Dion and Bruno Fuchs and Tim Damron and Steven Gitelis and Ronald Irwin and Mary O'Connor and Herbert Schwartz and Scully, {Sean P.} and Rock, {Michael G.} and Bolander, {Mark E.} and Gobinda Sarkar",
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AU - Dion, Norbert

AU - Fuchs, Bruno

AU - Damron, Tim

AU - Gitelis, Steven

AU - Irwin, Ronald

AU - O'Connor, Mary

AU - Schwartz, Herbert

AU - Scully, Sean P.

AU - Rock, Michael G.

AU - Bolander, Mark E.

AU - Sarkar, Gobinda

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N2 - The hSEP1 gene is the human homolog of yeast SEP1. Yeast SEP1 is a multifunctional gene that regulates a variety of nuclear and cytoplasmic functions including homologous recombination, meiosis, telomere maintenance, RNA metabolism and microtubule assembly. The function of hSEP1 is not known. We show loss or reduced expression of hSEP1 messenger RNA (mRNA) in three of four primary osteogenic sarcoma (OGS)-derived cell lines and in eight of nine OGS biopsy specimen. In addition, we find a heterozygous missence mutation (Valine 1484>Alanine) at a conserved amino acid in the primary OGS-derived cell line U2OS. Importantly, we identified a homozygous missense mutation involving a CG-dinucleotide leading to a change in a conserved amino acid, aspartic acid 1137 >asparagine, in the primary OGS-derived cell line, TE85. hSEP1 mRNA expression was nearly undetectable in TE85 and low in U2OS cell lines. None of these mutations were identified in 20 normal samples consisting of bone, cartilage and fibroblast. The hSEP1 gene is located in chromosome 3 at 3q25-26.1 between markers D3S1309 and D3S1569. An adjacent locus defined by the polymorphic markers D3S1212 and D3S1245 has previously been reported to undergo loss of heterozygosity (LOH) at a >70% frequency in OGS and claimed to harbor an important tumor suppressor gene in osteosarcoma. The homozygous mutation in the hSEP1 mRNA in TE85 cell line suggest that this gene itself is subject to LOH. Taken together, these results suggest that hSEP1 acts as a tumor suppressor gene in OGS.

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