title: Gene-expression analysis identifies novel RBL2/p130 target genes in endemic Burkitt lymphoma cell lines and primary tumors.
abstract: Burkitt lymphoma (BL) is a B-cell tumor whose characteristic gene aberration is the translocation t(8;14), which determines c-myc overexpression. Several genetic and epigenetic alterations other than c-myc overexpression have also been described in BL. It has been demonstrated that the RBL2/p130 gene, a member of the retinoblastoma family (pRbs), is mutated in BL cell lines and primary tumors. The aim of this study was to investigate the biologic effect of RBL2/p130 in BL cells and its possible role in lymphomagenesis. Therefore, we reintroduced a functional RBL2/p130 in BL cell lines where this gene was mutated. Our results demonstrated that RBL2/p130-transfected cells regain growth control. This suggests that RBL2/p130 may control the expression of several genes, which may be important for cell growth and viability. Gene-expression analysis revealed a modulation of several genes, including CGRRF1, RGS1, BTG1, TIA1, and PCDHA2, upon RBL2/p130 reintroduction. We then monitored their expression in primary tumors of endemic BL as well, demonstrating that their expression resembled those of the BL cell lines. In conclusion, these data suggest that, as RBL2/p130 modulates the expression of target genes, which are important for cell growth and viability, its inactivation may be relevant for the occurrence of BL.
authors.affiliation: Department of Human Pathology and Oncology, University of Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: De Falco
authors.forename: Eleonora
authors.initials: E
authors.lastname: Leucci
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Claudio
authors.forename: Anna
authors.initials: A
authors.lastname: Onnis
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cerino
authors.forename: Joshua
authors.initials: J
authors.lastname: Nyagol
authors.forename: Walter
authors.initials: W
authors.lastname: Mwanda
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.forename: Piero
authors.initials: P
authors.lastname: Tosi
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C493837:RBL2 protein, human; D050717:Retinoblastoma-Like Protein p130