TY - JOUR
T1 - The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma
AU - Zhang, Kunbo
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
N1 - Funding Information:
We thank Ms Kimberly Kasten for editorial assistance. This work has been funded by a grant from the Aircast Foundation (G.S) and the Orthopedics Research and Education Foundation (M.G.R., and G.S.).
PY - 2002/10/20
Y1 - 2002/10/20
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 (Valine1484>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 acid1137 >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.
AB - 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 (Valine1484>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 acid1137 >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.
KW - Biopsy
KW - Human homolog of yeast sep1
KW - Loss of heterozygosity
KW - Mutation
KW - Osteogenic sarcoma
KW - Tumor suppressor gene
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U2 - 10.1016/S0378-1119(02)00929-0
DO - 10.1016/S0378-1119(02)00929-0
M3 - Article
C2 - 12426100
AN - SCOPUS:18744363611
SN - 0378-1119
VL - 298
SP - 121
EP - 127
JO - Gene
JF - Gene
IS - 2
ER -