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.
The remaining 2 DLBCL models were germinal B-cell type, with characteristic alterations of GNA13, CREBBP, and EZH2, and chromosomal translocations involving IgH and either BCL2 or MYC Only 25% of the DLBCL PDX models harbored inactivating TP53 mutations, whereas 75% exhibited copy number alterations of TP53 or its upstream modifier, CDKN2A, consistent with the reported incidence and type of p53 pathway alterations in primary 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.
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.
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.
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.
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.
The colon adenocarcinomas had a mutation in MSH6 gene, DNA methylation in CDKN2A gene, and increased microsatellite instability (MSI), although these genetic changes were not recognized in either DLBCL or non-neoplastic UC mucosa.
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.
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.
(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.
We studied the HLA association, aberration p15, p16 and p73 promoter methylation and microsatellite instability in Chinese primary thyroid lymphoma patients to elucidate their relationship with AITD and the relationship between thyroid diffuse large cell lymphoma (DLCL) and marginal zone lymphomas (MZL).
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.
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.
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.
The prevalence of deletions at the D13S25 locus was significantly higher in CD5(+) DLBLs (4 of 12 [33%]) compared with CD5(-) DLBLs (4 of 42 [10%]), as were p16(INK4a) deletions (33% versus 8%).
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.
To elucidate the role of p53/p16(INK4a)/RB1 pathways in the tumorigenesis of primary central nervous system lymphomas (PCNSLs), we have analyzed p14(ARF), p16(INK4a), RB1, p21(Waf1), and p27(Kip1) status in a series of their 18 sporadic cases of diffuse large B-cell lymphoma, using methylation-specific PCR, differential PCR, and immunohistochemistry.