(1) To investigate, in primary nodal DLBCL, the expression of BMI1 and its association with clinical outcome and DLBCL signature; (2) to look for an association between BMI1 expression and the expression of its putative downstream targets p14ARF and p16INK4a.
Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study.
CDKN2A deletion or methylation was associated with more advanced age (P = 0.012) and normal hemoglobin (P = 0.05) but not with sex, FLIPI score, ECOG stage, LDH, performance status, number of involved nodal sites, B symptoms, histologic grade, the presence of a component of diffuse large B-cell lymphoma, proliferation index, or other pathologic factors.
CNAs of the CDKN2A-TP53-RB-E2F axis provide a structural basis for increased proliferation in DLBCL, predict outcome with current therapy, and suggest targeted treatment approaches.
Codeletion of CDKN2 and MTAP genes in a subset of non-Hodgkin's lymphoma may be associated with histologic transformation from low-grade to diffuse large-cell lymphoma.
Cyclin D3 overexpression and p16INK4A/pRb aberrations were mutually exclusive, supporting an oncogenic role for cyclin D3 in DLCL. p16INK4A inactivation, cyclin D3 overexpression, or aberrant pRb expression was identified in 18 of 34 DLCLs (53%).
Finally, when searching for genomic imbalances that affect patients' prognosis, we found that 9p21 loss (p16(INK4a) locus) marks the most aggressive type of DLBCL.
Identification of loss of p16 expression and upregulation of MDR-1 as genetic events resulting from two novel chromosomal translocations found in a plasmablastic lymphoma of the uterus.
In the present study, the methylation status of the promoter regions of protein tyrosine phosphatase (PTPN) 6, DAPK, and p16 were studied using methylation-specific polymerase chain reaction (MSP) in 26 diffuse large B cell lymphoma (DLBCL) lymphomas.
Interestingly, the methylation frequency of the CDH13 gene was comparable to those of the tumor suppressor genes p15 (68%) and p16 (74%) detected in B-DLCLs.
Loss of heterozygosity in regions 5q21 (APC gene locus), 9p21 (INK4A/ARF), 13q14 (RB), and 17p13 (p53) and allelic imbalances in 2p16, 6p23, and 12p12-13 occurred exclusively in DLBCL.
Loss-of-function mutations and copy number alterations in the tumor suppressors TP53 (diffuse large B-cell and follicular lymphoma), CDKN2A (diffuse large B-cell and marginal zone lymphoma), PTEN (diffuse large B-cell lymphoma), ATM (diffuse large B-cell lymphoma), and NF1 (diffuse large B-cell lymphoma), and gain-of-function mutations in the oncogenes HRAS (follicular lymphoma) and NRAS (diffuse large B-cell lymphoma) were also observed.
Molecular characterization of 9p21 deletions shows a minimal common deleted region removing CDKN2A exon 1 and CDKN2B exon 2 in diffuse large B-cell lymphomas.
Of the 9 matched pairs of LGFCL and progressed DLCL with interpretable immunohistochemical staining, 9 of 9 (100%) of the LGFCL showed diffuse reactivity for p16.
Our results suggest that hypermethylation of the p16 promoter indicates a poor prognosis in high-intermediate-risk and high-risk DLBCL patients, and may be a useful marker for selection of appropriate treatment when used in conjunction with the IPI.
P53 overexpression (P = 0.008) and a high proliferation index [Ki-67] (P = 0.00042) were significantly associated with gastric DLBCL, but no statistically significant difference was observed in P16 expression (p = 0.108) between gastric DLBCL and gastric MALT.
Patients with FL and high p14ARF expression had a significantly shorter survival time while survival for patients with DLBCL and increased p14ARF expression tended to be longer.
Patients with nodal diffuse large B-cell lymphomas (DLBCL) at a single institute (n=44) were studied for methylation of tumor-related genes, MGMT, p15(INK4B), p16(INK4A), p16(INK4A), Mad2, TMS1/ASC, CASP8, and GSTP1.
Sequential samples of the indolent and transformed phase of three cases showed the presence of p16(INK4a) deletions in the Richter's syndrome but not in the CLL component of two cases, whereas in a follicular lymphoma the deletion was present in both the follicular tumor and in the diffuse large-cell lymphoma.