Interaction of DDB1 with NBS1 in a DNA Damage Checkpoint Pathway.

Various DNA damage checkpoint control mechanisms in eukaryotic cells help maintain genomic integrity. Among these, NBS1, a key component of the MRE11-RAD50-NBS1 (MRN) complex, is an essential protein involved in the DNA damage response (DDR). In this study, we discovered that DNA damage-binding protein 1 (DDB1) interacts with NBS1.

Proline-serine-threonine-repeat region of MDC1 mediates Chk1 phosphorylation and the DNA double-strand break repair.

MDC1, a mediator of DNA damage response, recruits other repair proteins on double-strand break (DSB) sites. MDC1 is necessary for activating checkpoint kinases Chk1 and Chk2. It is unclear whether Chk1 interacts with MDC1.

The mutation of BCOR is highly recurrent and oncogenic in mature T-cell lymphoma.

Background: BCOR acts as a corepressor of BCL6, a potent oncogenic protein in cancers of the lymphoid lineage. We have found the recurrent somatic mutation of BCOR occurred in mature T-cell lymphoma (TCL). The role of BCOR mutation in lymphoid malignancies is unknown.

Angioimmunoblastic T-cell lymphoma-like lymphadenopathy in mice transgenic for human with p.Gly17Val mutation.

A missense mutation in encoding p.Gly17 Val has been reported to occur frequently in angioimmunoblastic T-cell lymphoma (AITL). Here, we describe a murine model which expresses the human mutant gene product in a T-cell specific manner and develops AITL-like symptoms.

Anti-Cancer Effects of CKD-581, a Potent Histone Deacetylase Inhibitor against Diffuse Large B-Cell Lymphoma.

Double-hit lymphoma (DHL) and double-expressor lymphoma (DEL) are aggressive forms of lymphoma that require better treatments to improve patient outcomes. CKD-581 is a new histone deacetylase (HDAC) inhibitor that exhibited a better safety profile in clinical trials compared to other HDAC inhibitors. Here, we demonstrate that CKD-581 inhibited the class I-II HDAC family via histone H3 and tubulin acetylation.

Comparison of the Lymph2Cx Assay and Hans Algorithm in Determining the Cell-of-Origin of Diffuse Large B-Cell Lymphomas, Not Otherwise Specified.

In the era of precision medicine, accurate and reproducible assignment of cell-of-origin (COO) in diffuse large B-cell lymphoma patients has become important. The Lymph2Cx assay is accurately determining COO by analyzing RNA expression of 20 selected genes while the Hans algorithm based on immunohistochemistry is the most popular method for routine daily diagnosis. However, there are discrepancies between the 2 methods, which need to be evaluated for better correlation.

Correction: The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in followed by mutations in and .

[This corrects the article DOI: 10.18632/oncotarget.14928.

Targeted deep sequencing of gastric marginal zone lymphoma identified alterations of TRAF3 and TNFAIP3 that were mutually exclusive for MALT1 rearrangement.

Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue is a distinct entity in that Helicobacter pylori infection plays the most important causative role in the development of the disease. To investigate the genomic alteration in gastric marginal zone lymphoma that was resistant to the H. pylori eradication therapy, we analyzed 19 cases of the gastric marginal zone lymphoma using fluorescence in situ hybridization for MALT1, BCL10 rearrangement, and targeted sequencing using an Illumina platform.

Cell-of-origin of diffuse large B-cell lymphomas determined by the Lymph2Cx assay: better prognostic indicator than Hans algorithm.

Diffuse large B-cell lymphomas (DLBCLs) are clinically heterogeneous and need a biomarker that can predict the outcome of treatments accurately. To assess the prognostic significance of the cell-of-origin type for DLBCLs, we applied the Lymph2Cx assay using a NanoString gene expression platform on formalin-fixed paraffin wax-embedded pretreatment tissues obtained from 82 patients with de novo DLBCL, not otherwise specified. All patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as the first line of chemotherapy.

The mutational landscape of ocular marginal zone lymphoma identifies frequent alterations in TNFAIP3 followed by mutations in TBL1XR1 and CREBBP.

Ocular marginal zone lymphoma is a common type of low-grade B-cell lymphoma. To investigate the genomic changes that occur in ocular marginal zone lymphoma, we analyzed 10 cases of ocular marginal zone lymphoma using whole-genome and RNA sequencing and an additional 38 cases using targeted sequencing. Major genetic alterations affecting genes involved in nuclear factor (NF)-κB pathway activation (60%), chromatin modification and transcriptional regulation (44%), and B-cell differentiation (23%) were identified.

Prognostic impact of MYC protein expression in central nervous system diffuse large B-cell lymphoma: comparison with MYC rearrangement and MYC mRNA expression.

The prognostic role of MYC has been well documented in non-central nervous system diffuse large B-cell lymphoma; however, it remains controversial in central nervous system diffuse large B-cell lymphoma. To investigate the prognostic value of MYC, we analyzed the MYC protein expression by immunohistochemistry, mRNA expression by RNA in situ hybridization, and gene status by fluorescence in situ hybridization in 74 cases of central nervous system diffuse large B-cell lymphoma. Moreover, we examined the correlation between MYC translocation, mRNA expression, and protein expression.

Mdc1 modulates the interaction between TopBP1 and the MRN complex during DNA damage checkpoint responses.

TopBP1 has been identified as a direct activator of ATR and interacts with the Nbs1 subunit of the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. In this study, we show that Mdc1 associates with both TopBP1 and Nbs1 in egg extracts and human cells. We cloned a cDNA encoding the full-length version of Xenopus Mdc1.

Clonal relationships in recurrent B-cell lymphomas.

Immunoglobulin (Ig) gene rearrangements remain largely unmodified during the clonal expansion of neoplastic cells. We investigated the clonal relationships between lymphoma components at diagnosis and at relapse by analyzing Ig gene rearrangements. A BIOMED-2 multiplex polymerase chain reaction (PCR) assay was performed in 27 patients using formalin-fixed paraffin embedded tissues, with subsequent cloning and sequencing of the amplified Ig genes in 17 patients.

Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma.

CTLA4 and CD28 are co-regulatory receptors with opposite roles in T-cell signaling. By RNA sequencing, we identified a fusion between the two genes from partial gene duplication in a case of angioimmunoblastic T-cell lymphoma. The fusion gene, which codes for the extracellular domain of CTLA4 and the cytoplasmic region of CD28, is likely capable of transforming inhibitory signals into stimulatory signals for T-cell activation.

Microarray Gene-expression Profiling Analysis Comparing PCNSL and Non-CNS Diffuse Large B-Cell Lymphoma.

Aim: The purpose of the present study was to compare microarray gene-expression profiling data between primary central nervous system (CNS) lymphoma and non-CNS lymphomas.

Materials And Methods: We performed whole-genomic cDNA-mediated annealing, selection and ligation assay with 177 formalin-fixed paraffin-embedded tumor samples.

Results: We identified 20 differentially expressed genes out of which 5 were predominantly expressed in CNS DLBCL compared to non-CNS DLBCL (C16orf59, SLC16A9, HPDL, SPP1, and MAG).

Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type.

Extranodal NK/T-cell lymphoma nasal type (ENKL) is a rare type of non-Hodgkin lymphoma that more frequently occurs in East Asia and Latin America. Even though its molecular background has been discussed in the last few years, the current knowledge does not explain the disease pathogenesis in most cases of ENKL. Here, we performed multiple types of next-generation sequencing on 34 ENKL samples, including whole-exome sequencing (9 cancer tissues and 4 cancer cell lines), targeted sequencing (21 cancer tissues), and RNA sequencing (3 cancer tissues and 4 cancer cell lines).

Identification of Sestrin3 Involved in the In vitro Resistance of Colorectal Cancer Cells to Irinotecan.

Irinotecan, an analogue of camptothecin, is frequently used as a single agent or in combination with other anticancer drugs for the treatment of colorectal cancer. However, the drug resistance of tumors is a major obstacle to successful cancer treatment. In this study, we established that cells acquire chronic resistance to irinotecan.

Integrated copy number and gene expression profiling analysis of Epstein-Barr virus-positive diffuse large B-cell lymphoma.

Viral oncogenes and host immunosenescence have been suggested as causes of Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV + DLBCL) of the elderly. To investigate the molecular genetic basis of immune evasion and tumor outgrowth, we analyzed copy number alterations (CNAs) and gene expression profiles in EBV + DLBCL samples compared with EBV - DLBCL. There were relatively few genomic alterations in EBV + DLBCL compared with those detected in EBV-negative DLBCL.

The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.

Smad3 functions as an integrator of diverse signaling, including transforming growth factor β signaling and the function of Smad3 is complexly regulated by differential phosphorylation at various sites of Smad3. Despite the importance of Smad3 and its various phosphoisoforms, their prognostic significance has rarely been studied. In this study, we demonstrated the prognostic significance of Smad3, its phosphoisoforms, and Smad4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas.

TopBP1 and Claspin contribute to the radioresistance of lung cancer brain metastases.

Background: Radiation therapy is one of the most effective therapeutic tools for brain metastasis. However, it is inevitable that some cancer cells become resistant to radiation. This study is focused on the identification of genes associated with radioresistance in metastatic brain tumor from lung cancer and the functional examination of the selected genes with regards to altered sensitivity of cancer cells to radiation.

CD10 expression is enhanced by Twist1 and associated with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro and in vivo.

CD10 expression was identified as a contributor to cancer progression in several cancers; however, the exact biological significance and mechanism of CD10 expression remains unclear. In addition, CD10 expression in esophageal squamous cell carcinoma (ESCC) has not been studied. We investigated the relationship between CD10 and Twist1.

Overexpression of integrin αv correlates with poor prognosis in colorectal cancer.

Aims: Integrin αv subunits are involved in tumour angiogenesis and tumour progression in various types of cancers. Clinical trials evaluating agents targeting integrin αv are ongoing. Integrin αv expression has been reported in several cancers in association with tumour progression or poor survival.