Project description:Recently, a subset of MYC-translocation negative aggressive B-cell lymphomas resembling Burkitt lymphoma (BL) characterized by proximal gains and distal losses in the long arm of chromosome 11 has been described. In the 2016 revision of the WHO classification these MYC-translocation negative lymphomas have been introduced as new provisional entity designated “Burkitt-like lymphoma with 11q aberration” (MNBLL 11q). Here, we show a comprehensive flow-cytometry analysis of 10 MNBLL 11q cases, well characterized genetically and pathologically. Twenty-three cases of MYC-positive BL, including three cases carrying both MYC rearrangements and 11q aberration, served as controls. All MNBLL 11q were CD20+/CD10+/BCL6+/BCL2- /MUM1- /MYC+/EBV negative , presented a high proliferation rate and showed a three-year overall survival (80%) similar to BL patients, with no recurrence after the end of treatment. MNBLL 11q immunophenotype was similar to that of MYC-positive BL without and with 11q, except for less frequent CD38higher expression (10% MNBLL 11q vs 91% MYC-positive BL, p<0.001), less frequent diminished CD45 expression (90% vs 23%, p=0.001), and CD16/CD56 co-expression (60% vs 0%, p<0.001). Our findings suggest subtle but important differences in MNBLL 11q immunophenotypes and MYC-positive BLs, which could not only aid in the differential diagnosis but also in the understanding of the pathogenesis of MNBLL 11q.
Project description:Copy number analysis using Agilent 244k or 180k (Case9) arrays was performed for 8 MYC-negative B-cell lymphomas, with sex-matched control DNAs
Project description:Copy number analysis using Agilent 244k or 180k (Case9) arrays was performed for 8 MYC-negative B-cell lymphomas, with sex-matched control DNAs Agilent 244k (cases 4-7 and 10-12) and 180k (Case9) arrays
Project description:Background: High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) is a rare germinal centre lymphoma with a typical gain/loss pattern on chromosome 11q, but without MYC translocation and with some features resembling Burkitt lymphoma (BL) and HGBCLs or germinal centre derived diffuse large B-cell lymphoma, not otherwise specified (GCB-DLBCL-NOS). The microRNA expression profile of HGBCL-11q is not characterised. We aim to analyse miRNA expression profile in HGBCL-11q, BL and in GCB-DLBCL-NOS. Methods: Next generation sequencing (NGS)-based microRNA profiling was performed for HGBCL-11q (n=6), BL (n=8), and also GCB-DLBCL-NOS without (n=3) and with MYC rearrangement (MYC-R) (n=7). Results: We identified 39 and 64 miRNAs differentiating HGBCL-11q from BL, and from GCB-DLBCL-NOS without MYC-R, respectively. We found that the expression level of miR-223-3p, miR-193b-3p, miR-29b-3p and miR-146a-5p simultaneously differentiated HGBCL-11q from BL, as well as from GCB-DLBCL-NOS without MYC-R. We found higher miRNA profile heterogeneity in HGBCL-11q than in BL. The analysis of MYC-regulated miRNA showed different profile in HGBCL-11q and in BL but demonstrated separation of HGBCL-11q and BL from GCB-DLBCL-NOS cases. Conclusion: microRNA profile of HGBCL-11q is different than that of BL and of GCB-DLBCL-NOS but more heterogeneous compared to BL.
Project description:Burkitt-like lymphoma with 11q aberration (BLL-11q) is a new provisional category in the 2016 WHO classification. The limited number of reported cases does not allow to define whether this is a specific entity or it is a particular variant of other recognized categories such as Burkitt or diffuse large B-cell lymphoma. The genetic alterations involved in the pathogenesis of BLL-11Q are not known.
Project description:Burkitt-like lymphoma with 11q aberration (BLL-11q) is a new provisional category in the 2016 WHO classification. The limited number of reported cases does not allow to define whether this is a specific entity or it is a particular variant of other recognized categories such as Burkitt or diffuse large B-cell lymphoma. The genetic alterations involved in the pathogenesis of BLL-11Q are not known.
Project description:Burkitt-like lymphoma with 11q aberration (BLL-11q) is a new provisional category in the 2016 WHO classification. The limited number of reported cases does not allow to define whether this is a specific entity or it is a particular variant of other recognized categories such as Burkitt or diffuse large B-cell lymphoma. The genetic alterations involved in the pathogenesis of BLL-11Q are not known.
Project description:Oral squamous cell carcinoma (OSCC) is associated with high case-fatality. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we examined paired DNA from peripheral blood and tumor cells to assess genome-wide LOH and DNA copy number alteration (CNA) and their associations with risk factors, tumor characteristics, and disease-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p, and 11q that seem to play an important role in oral cancer biology and survival from this disease.
Project description:Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, overexpression of the BRCA1-∆11q splice variant has been shown to cause PARPi resistance. How cancer cells achieve increased BRCA1-∆11q expression has remained unclear. Using isogenic cells with different BRCA1 mutations, we show that reduction in HUWE1 leads to increased levels of BRCA1-∆11q and PARPi resistance. This effect is specific to cells able to express BRCA1-∆11q (e.g. BRCA1 exon 11 mutant cells) and is not seen in BRCA1 mutants that cannot express BRCA1-∆11q, nor in BRCA2 mutant cells. As well as increasing levels of BRCA1-∆11q protein in exon 11 mutant cells, HUWE1 silencing also restores RAD51 nuclear foci and platinum salt resistance. HUWE1 catalytic domain mutations were also seen in a case of PARPi resistant, BRCA1 exon 11 mutant, high grade serous ovarian cancer. These results suggest how elevated levels of BRCA1-∆11q and PARPi resistance can be achieved, identify HUWE1 as a candidate biomarker of PARPi resistance for assessment in future clinical trials and illustrate how some PARPi resistance mechanisms may only operate in patients with particular BRCA1 mutations.
Project description:Oral squamous cell carcinoma (OSCC) is associated with high case-fatality. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we examined paired DNA from peripheral blood and tumor cells to assess genome-wide LOH and DNA copy number alteration (CNA) and their associations with risk factors, tumor characteristics, and disease-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p, and 11q that seem to play an important role in oral cancer biology and survival from this disease. We used Affymetrix 6.0 SNP arrays to test paired DNA from peripheral blood and tumor cells isolated by laser capture microdissection from 75 patients with HPV-negative OSCC. Peripheral blood DNA is used as reference for CNA to LOH.