PMID- 20421449 OWN - NLM STAT- MEDLINE DCOM- 20100916 LR - 20211203 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 116 IP - 6 DP - 2010 Aug 12 TI - Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling. PG - 953-61 LID - 10.1182/blood-2010-01-263806 [doi] AB - The genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that probably account for the various survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high-resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes, such as CUL4A, ING1, and MCPH1, may affect the 2 crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation, and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL because decreased expression of its members MOBKL2A, MOBKL2B, and LATS2 was associated with inferior outcome, including an independent validation series of 32 MCLs. FAU - Hartmann, Elena M AU - Hartmann EM AD - Institute of Pathology, University of Wuerzburg, Josef-Schneider-Strasse 2, Wuerzburg, Germany. FAU - Campo, Elias AU - Campo E FAU - Wright, George AU - Wright G FAU - Lenz, Georg AU - Lenz G FAU - Salaverria, Itziar AU - Salaverria I FAU - Jares, Pedro AU - Jares P FAU - Xiao, Wenming AU - Xiao W FAU - Braziel, Rita M AU - Braziel RM FAU - Rimsza, Lisa M AU - Rimsza LM FAU - Chan, Wing-Chung AU - Chan WC FAU - Weisenburger, Dennis D AU - Weisenburger DD FAU - Delabie, Jan AU - Delabie J FAU - Jaffe, Elaine S AU - Jaffe ES FAU - Gascoyne, Randy D AU - Gascoyne RD FAU - Dave, Sandeep S AU - Dave SS FAU - Mueller-Hermelink, Hans-Konrad AU - Mueller-Hermelink HK FAU - Staudt, Louis M AU - Staudt LM FAU - Ott, German AU - Ott G FAU - Bea, Silvia AU - Bea S FAU - Rosenwald, Andreas AU - Rosenwald A LA - eng GR - U01 CA114778/CA/NCI NIH HHS/United States GR - 5 U01 CA114778-03/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100426 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (MOB2 protein, human) RN - 0 (Nerve Tissue Proteins) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.1.11 (LATS2 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM CIN - Blood. 2010 Aug 12;116(6):861-2. PMID: 20705764 MH - Adult MH - Aged MH - Aged, 80 and over MH - Algorithms MH - Female MH - Gene Dosage/*genetics MH - *Gene Expression Profiling MH - *Gene Expression Regulation, Neoplastic MH - Genes, Tumor Suppressor MH - Homozygote MH - Humans MH - Kaplan-Meier Estimate MH - Loss of Heterozygosity/genetics MH - Lymphoma, Mantle-Cell/*genetics/*mortality/pathology MH - Male MH - Middle Aged MH - Nerve Tissue Proteins/genetics/metabolism MH - Polymorphism, Single Nucleotide MH - Prognosis MH - Protein Serine-Threonine Kinases/genetics/metabolism MH - Signal Transduction/physiology MH - Tumor Suppressor Proteins/genetics/metabolism PMC - PMC2924229 EDAT- 2010/04/28 06:00 MHDA- 2010/09/18 06:00 PMCR- 2011/08/12 CRDT- 2010/04/28 06:00 PHST- 2010/04/28 06:00 [entrez] PHST- 2010/04/28 06:00 [pubmed] PHST- 2010/09/18 06:00 [medline] PHST- 2011/08/12 00:00 [pmc-release] AID - S0006-4971(20)34642-5 [pii] AID - 2010/263806 [pii] AID - 10.1182/blood-2010-01-263806 [doi] PST - ppublish SO - Blood. 2010 Aug 12;116(6):953-61. doi: 10.1182/blood-2010-01-263806. Epub 2010 Apr 26.