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 INK4a/ARF locus at chromosome 9p21 encodes two structurally and functionally distinct molecules with tumor-suppressive properties. p16INK4a controls cell cycle progression by inhibiting phosphorylation of the retinoblastoma protein (Rb), while ARF prevents MDM2-mediated degradation of p53. By using a panel of PCR-based methods, we have examined the status of the p16INK4a, ARF and p53 genes in 123 cases of non-Hodgkin's lymphoma (NHL) at diagnosis. Alterations of one or more of these genes were detected in seven of 36 (19%) cases with low- to intermediate-grade histology, and in 35 of 87 (40%) cases with aggressive histology. For the aggressive lymphomas, the Kaplan-Meier estimate of overall survival for cases with disruption of either p16INK4a or the ARF-p53 pathway was not different from cases with retention of both pathways (5 year survival 45% vs 35%; P= 0.85), suggesting that selective inactivation of one of the pathways does not significantly influence overall survival. By contrast, the 5-year survival was only 7% for cases with concurrent disruption of p16INK4a and the ARF-p53 pathway vs 38% for cases with retention of one or both pathways (P = 0.005). Similar results were obtained when the analysis was confined to diffuse large B cell lymphomas (P= 0.019). On stepwise multivariate regression analysis including factors from the international prognostic index, concurrent disruption of p16INK4a and the ARF-p53 pathway was an independent negative prognostic factor in NHL with aggressive histology (P = 0.006). Our results suggest that the compound status of the p16INK4a and ARF-p53 pathways is a major determinant of outcome in NHL.
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PMID:Concurrent disruption of p16INK4a and the ARF-p53 pathway predicts poor prognosis in aggressive non-Hodgkin's lymphoma. 1102 47

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