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Wen-Juan Luo

Publications and source records attributed to Wen-Juan Luo.

12 recordsLinked to original sources
PubMed2006

Loss of expression of Epstein-Barr virus nuclear antigen-2 correlates with a poor prognosis in cases of pyothorax-associated lymphoma.

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma, which develops in the pleural cavity of patients who have had pyothorax for over 20 years, and is strongly associated with Epstein-Barr virus (EBV) infection. The expression of latent genes, especially EBV nuclear antigen-2 (EBNA-2), influences the growth characteristics and malignant features of EBV-infected cells. Here, the effect of EBNA-2 expression on clinical features was examined in 13 cases of PAL. The EBNA-2 transcript was detected in 8 cases but was absent in 5. There was a significant difference in survival between patients with the transcripts and those without: the 1-year survival rate was 87.5 and 0%, respectively (p < 0.01). There was a discrepancy between EBNA-2 expression and EBNA promoter usage in 6 cases. The Cp/Wp promoter was used in 3 EBNA-2-negative cases, whereas the Qp promoter or multiple promoters were used in 3 EBNA-2-positive cases. Analysis of PAL cell lines provided a clue as to the mechanism underlying the discrepancy between EBNA-2 expression and EBNA promoter usage. Loss of EBNA-2 expression, irrespective of the latency pattern, is correlated with a poor prognosis, suggesting that down-regulation of the EBNA-2 expression could be selection pressure for the progression of PAL.

Aged↗
PubMed2006

Impairment of double-strand breaks repair and aberrant splicing of ATM and MRE11 in leukemia-lymphoma cell lines with microsatellite instability.

Mutations of DNA double-strand breaks (DSB) repair genes, ATM, MRE11, RAD50, NBS1 and ATR, are postulated to play a role in the development of gastrointestinal malignancies with an impaired mismatch repair (MMR) function. In the present study, mutations of these genes together with the presence of microsatellite instability (MSI) were examined in 50 leukemia-lymphoma cell lines. MSI was detected in 13 (26%) lines. Mutations of intronic mononucleotide repeats in ATM and MRE11 were found in nine and six lines, respectively, whereas mutations of mononucleotide repeats of RAD50 were found in only one line, and none were found in either NBS1 or ATR. Frequencies of ATM and MRE11 mutations were significantly higher in MSI-positive than MSI-negative lines. These mutations generated aberrant splicing in both genes. The intensity of the aberrant transcript of ATM (497del22) was stronger in five lines harboring mononucleotide mutations of 2 bp or more than in the lines without or with a 1-bp mutation. The intensity of the aberrant transcript of MRE11 (315del88) was stronger in four lines with mononucleotide mutations than in lines without. The expression levels of ATM and MRE11 transcripts in MSI-positive lines were significantly higher than those in MSI-negative lines. MSI-positive cell lines showed delay or abrogation of DSB repair. The present study suggests that impairment of the MMR system causes aberrant transcripts in the DSB repair genes ATM and MRE11. This might result in inactivation of the DSB repair system, thus inducing an acceleration of genome instability and accumulation of genetic damage.

Acid Anhydride Hydrolases↗
PubMed2006

Alterations in ATR in nasal NK/T-cell lymphoma and chronic active Epstein-Barr virus infection.

Nasal natural killer (NK)/T-cell lymphoma (NKTCL) and chronic active Epstein-Barr virus infection (CAEBV) are relatively frequent, especially in Asia, and are poor in prognosis. Both diseases are proliferative diseases of NK/T cells that show highly complicated karyotypes, suggesting the involvement of chromosomal instability. ATR is an important gene for DNA damage response and chromosomal stability. To evaluate the role of ATR gene alterations in the pathogenesis of NKTCL and CAEBV, the whole coding region of the ATR gene was examined in cell lines derived from NKTCL and CAEBV, as well as tumor samples from patients. ATR alterations were detected in two of eight NKTCL and in one of three CAEBV lines. Most aberrant transcripts observed were deletions resulting from aberrant splicing. ATR alterations were also detected in four of 10 NKTCL clinical samples. Both NKTCL and CAEBV cell lines with ATR alterations showed a delay or abrogation in repair of ionizing radiation-induced DNA double-strand breaks and ultraviolet-induced DNA single-strand breaks, and both exhibited a defect in p53 accumulation. These findings show that alterations in the ATR gene result in an abnormal response to DNA double-strand break and single-strand break repair, suggesting a role for ATR gene alterations in NKTCL lymphomagenesis.

Alternative Splicing↗
PubMed2005

Identification of Epstein-Barr virus integrated sites in lymphoblastoid cell line (IB4).

IB4 is a lymphoblastoid cell line frequently used for the functional analysis of the latent genes of EBV. Previous study indicated that EBV whole genome is integrated tandemly as the linear viral genome into host genome of IB4, although sites of integration have not been determined. Through cloning of the junctional regions between EBV and host genomes, one of the integration sites was identified on the BamHI-C fragments around oriP sequences and another on the EcoRI-I fragment. Both of the integration sites were located on the clone RP11-119H12 of chromosome 4q25 and separated approximately 6.5 kbp from each other. The integration sites identified were apart from the genes of the host genome, indicating that both host gene and EBV latent genes are not altered by the integration event.

Base Sequence↗
PubMed2005

Alterations of DNA damage-response genes ATM and ATR in pyothorax-associated lymphoma.

Pyothorax-associated lymphoma (PAL) is non-Hodgkin's lymphoma that develops from chronic inflammation. Free radicals and oxidative stress generated in the inflammatory lesions could cause DNA damage and thus provide a basis for lymphomagenesis. Ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) genes are responsive genes for DNA damage, therefore potential involvement of these genes in PAL lymphomagenesis was examined in eight PAL cell lines and clinical samples from five cases. ATM mutations were detected in five of eight PAL lines. All but one of these mutations affected the phosphatidylinositol 3-kinase domain, indicating the loss-of-function mutation of ATM gene. Heterozygous mutations of ATR were found in two of eight lines; one a missense and the other a truncation mutation. ATR mutations were also detected in two of five cases in clinical samples from PAL. PAL cells with ATR mutation showed a delay or abrogation in repair for ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) or ultraviolet (UV)-induced DNA single-strand breaks (SSBs), and exhibited a defect in p53 accumulation and failure in cell cycle checkpoint at G1-S phase. These findings showed that mutations of ATR gene result in failure for DNA DSB and SSB repair, suggesting the role of ATM and ATR gene mutations in PAL lymphomagenesis.

Aged↗
PubMed2004

Integration of Epstein-Barr virus into chromosome 6q15 of Burkitt lymphoma cell line (Raji) induces loss of BACH2 expression.

Epstein-Barr virus (EBV) initially isolated from cultured Burkitt lymphoma (BL) cells, is a well-known oncogenic virus. The Raji cell line was established from BL tissue and used for research worldwide. Previous study showed that each Raji cell contains an average of 50-60 EBV genome equivalents, and a significant proportion of the EBV genome is linearly integrated into host genome through BamHI-W close to the BamHI-Y fragment. However, a definitive EBV integration site in the chromosome has not been identified as yet. In this study, direct evidence that EBV DNA is integrated into the host genome was provided through cloning of the fragments containing nucleotide sequence of Raji integration sites. Integrated EBV DNA consisted of the BamHI-W fragment at one end and BamHI-D fragment at another end. Both junction sites were highly guanine/cytosine-rich. The BamHI-W fragment and the adjacent part of chromosome 6 showed 70% homology, while no homology was found between the BamHI-D and adjacent host sequences. EBV was present at intron 1 of the BACH2 gene located on chromosome 6q15. BACH2 was not expressed in the Raji cell line. Because BACH2 is a putative tumor suppressor gene, loss of its expression through EBV integration might contribute to lymphomagenesis.

Animals↗
PubMed2004

Epstein-Barr virus is integrated between REL and BCL-11A in American Burkitt lymphoma cell line (NAB-2).

Epstein-Barr virus (EBV) initially isolated from the cultured Burkitt lymphoma (BL) cells, is one of the well-known oncogenic virus. The NAB-2 line, which was established from a North American Burkitt's tumor, was indicated to contain one copy of EBV DNA as the integrated form into chromosome 2p13 of the host genome. To demonstrate the integration site of EBV directly, and to clarify the relation between the integration sites and the oncogenes, fragments containing the nucleotide sequence of NAB-2 integration sites were cloned. EBV was integrated via the terminal repeats (TR), and integration sites located in the clone RP11-440P5 on chromosome 2, between two oncogenes, REL and BCL11A, which is apart from approximately 350 kbp from each other. Expression level of REL in NAB-2 was increased. The flanking region of chromosome 2 at the bilateral junction sites showed no homology to the junction sites of EBV. The integration site 2p13 overlaps with common fragile site, FRA2E. NAB-2 cells expressed almost all latent genes but LMP-2A that flanks the TR, indicating the type III of latent infection of EBV. Integration event in NAB-2 might alter the regulation of the oncogenes and provide advantage for continuous cell proliferation.

Base Sequence↗
PubMed2003

Establishment and characterization of unique cell lines derived from pyothorax-associated lymphoma which develops in long-standing pyothorax and is strongly associated with Epstein-Barr virus infection.

Malignant lymphoma frequently develops in the pleural cavity of patients with over 20 years' history of pyothorax. The term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. We established four novel lymphoma cell lines (OPL-3, -4, -5, and -7) from four patients with PAL. Characteristics of the four cell lines are as follows: B-cell nature with defective expression of B-cell and T-cell surface antigens, monoclonal pattern of Epstein-Barr virus (EBV) infection in lymphoma cells (thus indicating an etiological role of EBV for lymphomagenesis), complicated chromosomal abnormalities with numerous structural and numerical abnormalities, and occasional but distinct genome instability. These abnormalities in cell character might be caused by the specific circumstances of PAL lymphomagenesis, i.e., chronic inflammation. Thus, PAL cell lines could be useful in analysis of molecular mechanisms leading to malignancy in chronic inflammation.

Aged↗
PubMed2003

Analysis of p53, K-ras, c-kit, and beta-catenin gene mutations in sinonasal NK/T cell lymphoma in northeast district of China.

Recently we reported the different frequencies of p53 and c-kit gene mutations among sinonasal NK/T cell lymphoma (NKTCL) in Korea, north China (Beijing), and Japan, suggesting some racial, environmental, or life-style differences as a possible cause of nasal tumorigenesis. In this study, gene mutations in p53, c-kit, K-ras, and beta-catenin gene were analyzed by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) followed by direct sequencing in 20 cases of sinonasal NKTCL from northeast China (Shen Yang). Age of patients ranged from 5 to 63 (median, 40.0) years. p53 gene mutations were found in eight of 20 cases (40%), with exon 4 involvement in 10% of cases. The majority was missense mutations and G:C to A:T transition was predominant. The frequency of the c-kit and K-ras gene mutations was low (5%), while that of the beta-catenin gene was six of 20 cases (30%). From these findings, it is concluded that nasal NKTCL in northeast China shared common features with that in Korea in the younger onset of disease compared to that in Japan and lower frequency of p53 gene mutations with infrequent exon 4 involvement compared to that in Japan and north China. These differences might be caused by migration of susceptible populations or some environmental confounding factors.

Adolescent↗
PubMed2002

Fas and Fas ligand gene mutations in Hashimoto's thyroiditis.

To clarify whether Fas and Fas ligand (FasL) mutations are involved in the pathogenesis of Hashimoto's thyroiditis (HT), we examined the open reading frame of Fas and FasL in 21 cases. Mutations of Fas and FasL genes were detected in 8 (38.1%) and 1 (4.8%) of 21 cases, respectively. All but one of the Fas mutations were frameshift mutations, which affect the cytoplasmic region (death domain) known to be involved in apoptotic signal transduction and thus could be loss-of-function mutations. FasL mutation in one case was a 46-bp deletion from nucleotide 349 to 394, which corresponded to exon 2. Lack of exon 2 results in a frameshift, which generates a stop codon at residue 128. This mutant encodes the protein that contains only a part of the intracellular domain, thus the abnormal protein might not be expressed on the cell surface. The cells with Fas mutations were confined to the mantle zone and the germinal center, as determined by microdissection methods. These findings suggest that the cells with Fas mutations might accumulate in those areas and might be involved in the pathogenesis of Hashimoto's thyroiditis.

Aged↗
PubMedDate not supplied

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