title: Disruption of chromosomal locus 1p36 differentially modulates TAp73 and ΔNp73 expression in follicular lymphoma.
abstract: The TP73 gene is located at the chromosome 1p36 locus that is commonly disrupted or deleted in follicular lymphoma (FL) with poor prognosis. Therefore, we analyzed the expression of the pro-apoptotic TAp73 and anti-apoptotic ΔNp73 isoforms in cases of FL with normal or abnormal 1p36. We observed a significant increase in ΔNp73 expression and ΔNp73:TAp73 ratio, lower expression of cleaved caspase-3 and a higher frequency of Ki-67 and proliferating cell nuclear antigen (PCNA) positive cells in cases of FL with abnormal 1p36. A negative correlation between the ΔNp73:TAp73 ratio and cleaved caspase-3 expression, and a positive correlation between ΔNp73 expression and Ki-67 or PCNA, were observed. The expression of TAp73 and its pro-apoptotic transcriptional targets BIM. PUMA and NOXA were significantly lower in FL compared to reactive follicular hyperplasia. Together, our data demonstrate that 1p36 disruption is associated with increased ΔNp73 expression, decreased apoptosis and increased proliferation in FL.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE , USA.
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Hassan
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Varney
authors.forename: Smrati
authors.initials: S
authors.lastname: Jain
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Singh
authors.forename: Bhavana J
authors.initials: BJ
authors.lastname: Dave
mesh_terms: D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C498702:PMAIP1 protein, human; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human
keywords: Chromosome 1p36; follicular lymphoma; p73 isoforms