Background: Over 1100 genes have been annotated for human chromosome 9, including disease genes implicated in inflammation, atherosclerosis, cancer and neurodegeneration. The serine palmitoyltransferase-1, SPTLC1, gen...Background: Over 1100 genes have been annotated for human chromosome 9, including disease genes implicated in inflammation, atherosclerosis, cancer and neurodegeneration. The serine palmitoyltransferase-1, SPTLC1, gene is at the 9q22.2 cytogenetic band, a high G+C content region with common genetic alterations sufficient to modify cellular behavior. The sequence is highly conserved among diverse species from bacteria to humans, including a recently discovered 126 nucleotide alternate open reading frame, AltORF. The protein encoded by the reading frames has domains of biological interest and considerable overlapping molecular functions associated with cellular behavior and cancer progression. Methods: Here we examined molecular features of SPTLC1 in a group of inflammation associated cancer cell lines SKN-SH, MDA-PCa, Glioma LN18, PC3 and 647V. Subcellular localization of SPTLC1 was assessed by immunofluorescence microscopy and recombinant green fluorescent protein expression. In addition, PCR, DNA sequencing and bioinformatics analysis were used for molecular profiling of the SPTLC1 genomic and reverse transcribed cDNA fragments. Results: SPTLC1 is detected in all cell lines examined, with intense peri-nuclear staining, consistent with localization in the cytoplasm. Genomic DNA sample, but not the cD NA of SKN cells could be amplified with an AltORF primer set. The PC3 and MDA-PCa cancer cell lines which are both of prostate origin, show differences in SPTLC1 PCR amplification. Similar levels of SPTLC1 AltORF transcripts were detected by quantitative RT-PCR in all cell lines, except the PC3 cell line with low transcript level whose cDNA did not generate nucleotide base sequence information. Conclusions: This is the first reported transcriptional expression of the SPTLC1 AltORF for the inflammation associated human cancer cell lines. Interestingly, it is proximate of oncogenic cancer susceptibility genes and distal of tumor suppressor genes, the high content of short nucleotide repeats in the SPTLC1 AltORF sequence suggesting the region may be genetically unstable. This nominal functional genomics report on the human SPTLC1 AltORF will contribute to compiling a more detailed SPTLC1 gene ontology and is expected to help shed more insight into unique molecular attributes of SPTLC1 in the context of cancer cell behavior, malignant progression and the design of treatment for inflammation associated cancers.展开更多
OBJECTIVE: To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation betw...OBJECTIVE: To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation between LOH and clinicopathologic parameters and/or Epstein-Barr virus (EBV) infection in NPC. METHODS: Sixty cases of NPC were studied using polymerase chain reaction based microsatellite analysis with genescan and genotyping techniques. RESULTS: LOH was detected on 13q in 78% of NPC tumors, high frequency LOH loci (more than 30%) clustered to 13q12.3-q14.3 and 13q32. On chromosome 14q, LOH was detected in 80% of NPC tumors; high frequency LOH loci clustered to 14q11-q13, 14q21-q24 and 14q32. High frequency LOH at 13q31-q32 correlated with a lower level of EBV infection; LOH on chromosome 14q was closely associated with poor differentiation of NPC tumor cells. CONCLUSION: Our results suggest that in NPC, LOH on chromosome 13q and 14q are common genetic events, and putative tumor suppressor genes (TSG) residing in these regions may be involved in tumorigenesis.展开更多
Spindle is a specific substructure in cell during meiosis and gamete maturity division and its structure and function directly influence the development, differentiation, growth and reproduction of individuals. Recent...Spindle is a specific substructure in cell during meiosis and gamete maturity division and its structure and function directly influence the development, differentiation, growth and reproduction of individuals. Recent researches also show that mouse Mos/MAPK pathway is tightly related to spindiin phosphorylation. We report that (i) a novel gene encoding a putative human spindlin (SPIN) has been cloned, which is highly homologous to mouse Spin; (ii) tissue expression pattern of SPIN shows that SPIN is highly expressed as a 4.8 kb transcript in ovary, testis, heart, brain, kidney, pancreas, placenta and spleen, also with a specific 2.0 kb transcript in testis, but there is no hybridization band in thymus and small intestine, and (iii) SPIN has been mapped to human chromosome 9q22.1-22.3 by Radiation Hybrid Mapping. This novel gene was registered in GenBank as SPIN with accession number AF087864.展开更多
目的:抑癌基因的杂合缺失(loss of heterozygosity,LOH)被认为是结直肠癌形成的关键步骤之一。本实验研究了结直肠癌1号染色体短臂杂合的缺失情况,并探讨其临床意义。方法:选取11个微卫星DNA标记与83例结直肠癌病例的肿瘤和正常组织进行...目的:抑癌基因的杂合缺失(loss of heterozygosity,LOH)被认为是结直肠癌形成的关键步骤之一。本实验研究了结直肠癌1号染色体短臂杂合的缺失情况,并探讨其临床意义。方法:选取11个微卫星DNA标记与83例结直肠癌病例的肿瘤和正常组织进行PCR。PCR产物在ABIPrism377自动荧光测序仪上进行电泳,以GeneScan3.1和Genotyper2.1软件进行遗传位点扫描以及杂合缺失分析。结果:1号染色体短臂的平均杂合缺失率为18.00%,D1S468(1p36.33-36.31)位点的杂合缺失率最高,达36.54%。D1S2726位点的杂合缺失现象主要存在于直肠癌,缺失率为28.57%(6/21),而结肠癌的缺失率为0.00%(0/33),二者差异具统计学意义(P=0.002)。结论:在1号染色体短臂上可能存在与结直肠癌发生相关的抑癌基因,位于1p36.33-36.31这个区域。展开更多
文摘Background: Over 1100 genes have been annotated for human chromosome 9, including disease genes implicated in inflammation, atherosclerosis, cancer and neurodegeneration. The serine palmitoyltransferase-1, SPTLC1, gene is at the 9q22.2 cytogenetic band, a high G+C content region with common genetic alterations sufficient to modify cellular behavior. The sequence is highly conserved among diverse species from bacteria to humans, including a recently discovered 126 nucleotide alternate open reading frame, AltORF. The protein encoded by the reading frames has domains of biological interest and considerable overlapping molecular functions associated with cellular behavior and cancer progression. Methods: Here we examined molecular features of SPTLC1 in a group of inflammation associated cancer cell lines SKN-SH, MDA-PCa, Glioma LN18, PC3 and 647V. Subcellular localization of SPTLC1 was assessed by immunofluorescence microscopy and recombinant green fluorescent protein expression. In addition, PCR, DNA sequencing and bioinformatics analysis were used for molecular profiling of the SPTLC1 genomic and reverse transcribed cDNA fragments. Results: SPTLC1 is detected in all cell lines examined, with intense peri-nuclear staining, consistent with localization in the cytoplasm. Genomic DNA sample, but not the cD NA of SKN cells could be amplified with an AltORF primer set. The PC3 and MDA-PCa cancer cell lines which are both of prostate origin, show differences in SPTLC1 PCR amplification. Similar levels of SPTLC1 AltORF transcripts were detected by quantitative RT-PCR in all cell lines, except the PC3 cell line with low transcript level whose cDNA did not generate nucleotide base sequence information. Conclusions: This is the first reported transcriptional expression of the SPTLC1 AltORF for the inflammation associated human cancer cell lines. Interestingly, it is proximate of oncogenic cancer susceptibility genes and distal of tumor suppressor genes, the high content of short nucleotide repeats in the SPTLC1 AltORF sequence suggesting the region may be genetically unstable. This nominal functional genomics report on the human SPTLC1 AltORF will contribute to compiling a more detailed SPTLC1 gene ontology and is expected to help shed more insight into unique molecular attributes of SPTLC1 in the context of cancer cell behavior, malignant progression and the design of treatment for inflammation associated cancers.
文摘OBJECTIVE: To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation between LOH and clinicopathologic parameters and/or Epstein-Barr virus (EBV) infection in NPC. METHODS: Sixty cases of NPC were studied using polymerase chain reaction based microsatellite analysis with genescan and genotyping techniques. RESULTS: LOH was detected on 13q in 78% of NPC tumors, high frequency LOH loci (more than 30%) clustered to 13q12.3-q14.3 and 13q32. On chromosome 14q, LOH was detected in 80% of NPC tumors; high frequency LOH loci clustered to 14q11-q13, 14q21-q24 and 14q32. High frequency LOH at 13q31-q32 correlated with a lower level of EBV infection; LOH on chromosome 14q was closely associated with poor differentiation of NPC tumor cells. CONCLUSION: Our results suggest that in NPC, LOH on chromosome 13q and 14q are common genetic events, and putative tumor suppressor genes (TSG) residing in these regions may be involved in tumorigenesis.
文摘Spindle is a specific substructure in cell during meiosis and gamete maturity division and its structure and function directly influence the development, differentiation, growth and reproduction of individuals. Recent researches also show that mouse Mos/MAPK pathway is tightly related to spindiin phosphorylation. We report that (i) a novel gene encoding a putative human spindlin (SPIN) has been cloned, which is highly homologous to mouse Spin; (ii) tissue expression pattern of SPIN shows that SPIN is highly expressed as a 4.8 kb transcript in ovary, testis, heart, brain, kidney, pancreas, placenta and spleen, also with a specific 2.0 kb transcript in testis, but there is no hybridization band in thymus and small intestine, and (iii) SPIN has been mapped to human chromosome 9q22.1-22.3 by Radiation Hybrid Mapping. This novel gene was registered in GenBank as SPIN with accession number AF087864.
基金Supported by the National Natural Science Foundation of China (30170394) the Special Fund for Promotion of Education Ministry of Science P.R.C (985) and "973"Foundation of China (001cb51010201).
文摘目的:抑癌基因的杂合缺失(loss of heterozygosity,LOH)被认为是结直肠癌形成的关键步骤之一。本实验研究了结直肠癌1号染色体短臂杂合的缺失情况,并探讨其临床意义。方法:选取11个微卫星DNA标记与83例结直肠癌病例的肿瘤和正常组织进行PCR。PCR产物在ABIPrism377自动荧光测序仪上进行电泳,以GeneScan3.1和Genotyper2.1软件进行遗传位点扫描以及杂合缺失分析。结果:1号染色体短臂的平均杂合缺失率为18.00%,D1S468(1p36.33-36.31)位点的杂合缺失率最高,达36.54%。D1S2726位点的杂合缺失现象主要存在于直肠癌,缺失率为28.57%(6/21),而结肠癌的缺失率为0.00%(0/33),二者差异具统计学意义(P=0.002)。结论:在1号染色体短臂上可能存在与结直肠癌发生相关的抑癌基因,位于1p36.33-36.31这个区域。
