title: High resolution genome-wide analysis of chromosomal alterations in Burkitt's lymphoma.
abstract: Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27), 13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27), 17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal critical regions (MCR), (range 0.04-71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 <89.58-96.81> MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96-61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 <60.43-60.53> that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies.
authors.affiliation: CNRS, FRE2939, Génomique Cellulaire des Cancers, Institut Gustave Roussy (IGR), Villejuif, France.
authors.forename: Saloua
authors.initials: S
authors.lastname: Toujani
authors.forename: Philippe
authors.initials: P
authors.lastname: Dessen
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ithzar
authors.forename: Gisèle
authors.initials: G
authors.lastname: Danglot
authors.forename: Catherine
authors.initials: C
authors.lastname: Richon
authors.forename: Yegor
authors.initials: Y
authors.lastname: Vassetzky
authors.forename: Thomas
authors.initials: T
authors.lastname: Robert
authors.forename: Vladimir
authors.initials: V
authors.lastname: Lazar
authors.forename: Jacques
authors.initials: J
authors.lastname: Bosq
authors.forename: Lydie
authors.initials: L
authors.lastname: Da Costa
authors.forename: Christine
authors.initials: C
authors.lastname: Pérot
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.forename: Catherine
authors.initials: C
authors.lastname: Patte
authors.forename: Jöelle
authors.initials: J
authors.lastname: Wiels
authors.forename: Alain
authors.initials: A
authors.lastname: Bernheim
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D003582:Cytogenetics; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D007136:Immunoglobulins; D009841:Oligonucleotides