Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CDKN2A gene located on chromosome region 9p21 encodes the cyclin-dependent kinase-4 inhibitor p16/INK4A, a negative cell cycle regulator. We analyzed p16/INK4A expression in different types of non-Hodgkin's lymphoma to determine whether the absence of this protein is involved in lymphomagenesis, while also trying to characterize the genetic events underlying this p16/INK4A loss. To this end, we investigated the levels of p16/INK4A protein using immunohistochemical techniques in 153 cases of non-Hodgkin's lymphoma, using as reference the levels found in reactive lymphoid tissue. The existence of gene mutation, CpG island methylation, and allelic loss were investigated in a subset of 26 cases, using single-strand conformational polymorphism and direct sequencing, Southern Blot, polymerase chain reaction, and microsatellite analysis, respectively. Loss of p16/INK4A expression was detected in 41 of the 112 non-Hodgkin's lymphomas studied (37%), all of which corresponded to high-grade tumors. This loss of p16/INK4A was found more frequently in cases showing tumor progression from mucosa-associated lymphoid tissue low-grade lymphomas (31 of 37) or follicular lymphomas (4 of 4) into diffuse large B-cell lymphomas. Analysis of the status of the p16/INK4A gene showed different genetic alterations (methylation of the 5'-CpG island of the p16/INK4A gene, 6 of 23 cases; allelic loss at 9p21, 3 of 16 cases; and nonsense mutation, 1 of 26 cases). In all cases, these events were associated with loss of the p16/INK4A protein. No case that preserved protein expression contained any genetic change. Our results demonstrate that p16/INK4A loss of expression contributes to tumor progression in lymphomas. The most frequent genetic alterations found were 5'-CpG island methylation and allelic loss.
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PMID:Loss of p16/INK4A protein expression in non-Hodgkin's lymphomas is a frequent finding associated with tumor progression. 973 37

Human herpesvirus 8 (HHV-8)-associated primary effusion lymphoma is a rare non-Hodgkin's lymphoma often associated with Epstein-Barr virus (EBV) infection. Mutations in TP53, PTEN, PIK3CA, CTNNB1/beta-catenin genes and deletion of CDKN2A-ARF (p14(ARF)-p16(NK4a I) ) locus were investigated in sixteen primary primary effusion lymphoma tumors and seven primary effusion lymphoma cell lines using PCR and sequencing. TP53 mutations were detected in one primary primary effusion lymphoma tumor (6.2%) and two primary effusion lymphoma cell lines (28.6%). BC-3 and BCP-1 cell lines showed PTEN gene mutations, associated with a loss of PTEN protein expression in both cases. No mutations were detected in PIK3CA and CTNNB1/beta-catenin hotspot sequences. Only BC-3 contained a homozygous deletion of CDKN2A-ARF locus. Although detected at a higher frequency in primary effusion lymphoma cell lines than in primary primary effusion lymphoma tumors, TP53 and/or PTEN mutations, as well as deletion of CDKN2A-ARF locus are uncommon in primary effusion lymphoma, and are found to correlate with the EBV-negative status of primary effusion lymphoma tumors.
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PMID:Mutational analysis of TP53, PTEN, PIK3CA and CTNNB1/beta-catenin genes in human herpesvirus 8-associated primary effusion lymphoma. 1960 68

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and highly aggressive subtype of non-Hodgkin's lymphoma. It commonly presents as rapidly-growing, painless lymphadenopathy (LAD). DLBCL presenting in leukemic-phase is rare, with fewer than 40 cases published. Chemotherapy remains the standard approach, although selecting the correct regimen has become more perplexing in patients with CDKN2A mutations. Patients with MLL- and CDKN2A-positive DLBCL may benefit from therapy with a dose-adjusted regimen of rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) compared to traditional rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). Herein, we report a case of leukemic-phase DLBCL presenting as a cutaneous eruption of the bilateral lower extremities, which has not been previously reported in the literature.
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PMID:Infiltrative Rash Secondary to Leukemic-Phase Diffuse Large B-Cell Lymphoma With t(14;18), CDKN2A and MLL Deletion. 3230 Apr