Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL.

Brain Pathology
J M CobbersG Reifenberger

Abstract

Twenty primary central nervous system lymphomas (PCNSL) from immunocompetent patients (nineteen B-cell lymphomas and one T-cell lymphoma) were investigated for genetic alterations and/or expression of the genes BCL2, CCND1, CDK4, CDKN1A, CDKN2A, MDM2, MYC, RB1, REL, and TP53. The gene found to be altered most frequently was CDKN2A. Eight tumors (40%) showed homozygous and two tumors (10%) hemizygous CDKN2A deletions. Furthermore, methylation analysis of six PCNSL without homozygous CDKN2A loss revealed methylation of the CpG island within exon 1 of CDKN2A in three instances. Reverse transcription PCR analysis of CDKN2A mRNA expression was performed for 11 tumors and showed either no or weak signals. Similarly, immunocytochemistry for the CDKN2A gene product (p16) remained either completely negative or showed expression restricted to single tumor cells. None of the PCNSL showed amplification of CDK4. Similarly, investigation of CCND1 revealed no amplification, rearrangement or overexpression. The retinoblastoma protein was strongly expressed in all tumors. Only one PCNSL showed a mutation of the TP53 gene, i.e., a missense mutation at codon 248 (CGG to TGG:Arg to Trp). No evidence of BCL2 gene rearrangement was found in 11 tumor...Continue Reading

References

Apr 1, 1992·Brain Pathology·J W Grant, P G Isaacson
Aug 1, 1992·Leukemia & Lymphoma·A M GinsbergJ Cossman
Nov 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C L RosenbergA Arnold
Jun 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·G GaidanoR Dalla-Favera
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J LacyW C Summers
Dec 1, 1988·Cancer·N L EbyP C Burger
Nov 5, 1987·The New England Journal of Medicine·L M WeissM L Cleary
Jun 21, 1985·Science·Y TsujimotoC M Croce
Dec 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·R Dalla-FaveraC M Croce
Oct 1, 1994·Genes, Chromosomes & Cancer·J HeC D James
Feb 24, 1995·Cell·E M MiyashitaD A Thorley-Lawson
Apr 4, 1995·Biochimica Et Biophysica Acta·E TulchinskyE Lukanidin
Oct 20, 1995·International Journal of Cancer. Journal International Du Cancer·H X AnH G Bender
Jul 1, 1995·British Journal of Cancer·D J AdamsonN E Haites
Oct 1, 1994·British Journal of Haematology·B QuesnelP Fenaux
Jan 1, 1995·Journal of Neuropathology and Experimental Neurology·S B HunterC D James
Jan 1, 1994·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K A LeeM H Goyns
Feb 1, 1994·British Journal of Haematology·S A RidgeL M Wiedemann
Feb 1, 1994·International Journal of Cancer. Journal International Du Cancer·E CesarmanD M Knowles
Jan 1, 1995·Journal of Neuro-oncology·K A Jellinger, W Paulus
Jul 1, 1996·Japanese Journal of Cancer Research : Gann·T KumanishiK Washiyama
Nov 1, 1995·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·F Hoppe-Seyler, K Butz
Oct 4, 1996·Cell·P A Baeuerle, D Baltimore
Dec 6, 1996·Science·C J Sherr
Jul 1, 1996·Journal of Neuropathology and Experimental Neurology·J ReifenbergerG Reifenberger
Oct 1, 1996·Leukemia & Lymphoma·M Heyman, S Einhorn
May 26, 1998·Journal of Neuropathology and Experimental Neurology·K L BurnsD N Louis

❮ Previous
Next ❯

Citations

Mar 29, 2001·The Journal of Pathology·N SeemannW Paulus
Mar 18, 2003·International Journal of Cancer. Journal International Du Cancer·Markus J RiemenschneiderGuido Reifenberger
Jul 22, 2006·International Journal of Cancer. Journal International Du Cancer·Linda C ChuJames G Herman
Aug 22, 2007·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·Maurilio PonzoniFrancesco Bertoni
May 9, 2009·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Liang-Hong TengQing-Zhong Xu
Nov 19, 2013·Acta Neuropathologica·Martina DeckertReiner Siebert
Sep 20, 2008·Blood·Manuel Montesinos-RongenMartina Deckert
Nov 14, 2018·Neuro-oncology·Christian GrommesTracy T Batchelor
Jul 12, 2002·Genes, Chromosomes & Cancer·Bertrand ActorRuthild G Weber
Sep 8, 2000·The American Journal of Surgical Pathology·J MisdrajiN L Harris
Nov 26, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Eyas M HattabMousa A Al-Abbadi
Jun 30, 2009·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Alain P AlgaziJames L Rubenstein
Sep 21, 2018·American Society of Clinical Oncology Educational Book·Joe S Mendez, Christian Grommes
May 18, 2019·American Society of Clinical Oncology Educational Book·Andrés J M FerreriJames L Rubenstein
Oct 22, 2002·Journal of Neuropathology and Experimental Neurology·Manuel Montesinos-RongenReiner Siebert
Oct 16, 2004·International Journal of Hematology·Tomohiro Kinoshita
Dec 3, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ilaria IacobucciGiovanni Martinelli
Jul 28, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alberto Gonzalez-AguilarKhê Hoang-Xuan
May 12, 2020·Surgical Pathology Clinics·David M Meredith

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

CNS Lymphoma

In CNS lymphoma, cancerous cells from lymph tissues or other parts of the body form tumors in the brain and/or spinal cord. Here is the latest research on this rare non-Hodgkin lymphoma.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.