Anti-BCL10 monoclonal antibody, clone 262

Ovarian lymphoma, whether a primary or secondary condition, is very rare. Little is known about its genetic aberrations. Here, we reviewed the clinical, morphological and immunohistochemical characteristics of nine ovarian diffuse large B-cell lymphoma (DLBCL) cases and performed fluorescence in situ hybridisation (FISH) analysis to detect MYC, BCL2 and BCL6 translocations. We also performed whole exome sequencing analysis to determine their genomic features compared with those of conventional extranodal DLBCL. The results showed that six of nine cases were bilateral and three cases were left-sided. Histologically, the tumour cells were homogeneous and a starry-sky pattern was very common in ovarian DLBCL (Burkitt-like). Immunohistochemically, most of the cases (7/9) were germinal centre B-cell-like (GCB) subtype, and dual expression of MYC and BCL2 was found in three cases of ovarian DLBCL. A double-hit (involving MYC and BCL6) phenotype was found in one case of ovarian DLBCL (GCB subtype). Sequencing analysis revealed that NOTCH4, NCOR2, BCL10 and CARD11 were frequently mutated both in ovarian DLBCL and conventional extranodal DLBCL. COL27A1, PRKCB, HLA-A, NOTCH3 and HDAC4 mutations were found only in ovarian DLBCL but not in conventional DLBCL, and NOTCH3 and HDAC4 mutations were only identified in the GCB subtype. Furthermore, several signalling pathways including the B-cell receptor, Epstein-Barr virus infection, HTLV-1 infection, Notch, PI3K-AKT and mTOR were found to be involved in ovarian DLBCL. Our results broaden the understanding of the clinicopathological and molecular characteristics of ovarian DLBCL and compare their genetic features to those of conventional extranodal DLBCL for the first time.

We aimed to investigate the clinical significance of the expression of novel scaffold protein CARMA3 in non-small-cell lung cancer (NSCLC) and the biological function of CARMA3 in NSCLC cell lines. We observed moderate to high CARMA3 staining in 68.8% of 141 NSCLC specimens compared to corresponding normal tissues. The overexpression of CARMA3 was significantly correlated with TNM stage (P = 0.022) and tumor status (P = 0.013). CARMA3 upregulation also correlated with a shorter survival rate of patients of nodal status N0 (P = 0.042) as well as the expression of epidermal growth factor receptor (EGFR) (P = 0.009). In EGFR mutation positive cases, CARMA3 expression was much higher (87.5%) compared to non-mutation cases (66.1%). In addition, we observed that knockdown of CARMA3 inhibits tumor cell proliferation and invasion, and induces cell cycle arrest at the boundary between the G1 and S phase. We further demonstrated a direct link between CARMA3 and NF-kappa B activation. The change of biological behavior in CARMA3 knockdown cells may be NF-kappa B-related. Our findings demonstrated, for the first time, that CARMA3 was overexpressed in NSCLC and correlated with lung cancer progression, EGFR expression, and EGFR mutation. CARMA3 could serve as a potential companion drug target, along with NF-kappa B and EGFR in EGFR-mutant lung cancers.