title: A Novel Non-Immunoglobulin (non-Ig)/BCL6 Translocation in Diffuse Large B-Cell Lymphoma Involving Chromosome 10q11.21 Loci and Review on Clinical Consequences of BCL6 Rearrangements.
abstract: BCL6 rearrangements (3q27) are the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL), with numerous immunoglobulin (Ig) and non-Ig genes as partners. In DLBCL, the translocations occur predominantly in the "major breakpoint region" encompassing the first noncoding exon and a part of the first intron of BCL6; few cases with "alternative breakpoint cluster" located 245-285 kb 5' BCL6 were also described. The regulatory sequences of known Ig and non-Ig partners replace the 5' untranslated region of the BCL6 in the same transcriptional orientation. Contrary to Ig/BCL6 fusions typical by high BCL6 gene expression, in non-Ig/BCL6 translocations were observed unexpectedly low BCL6 mRNA levels. From the clinical point of view, the survival rate of DLBCL patients with non-Ig partners is inferior to those with Ig/BCL6 translocations, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator. Hereby we provide comprehensive information about known non-Ig translocation partners and clinical consequences of BCL6 rearrangements in DLBCL. Moreover, we describe a novel reciprocal translocation t(3;10) in refractory patient with DLBCL with the breaking points at 5' untranslated region of BCL6 and 5' untranslated region of the RASGEF1A gene on chromosome 10q11.21 loci; this rearrangement was associated with low BCL6 and RASGEF1A gene expressions. Our patient harbouring dual chromosomal rearrangement involving BCL2 and BCL6 genes relapsed three-times and died soon; thus, further supporting the notion that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. There is evidence of prognostic value of BCL6 rearrangements also in rituximab era.
authors: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic. marie.jarosova@fnol.cz.
authors: Marie
authors: M
authors: Jarosova
authors: Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Eva
authors: E
authors: Kriegova
authors: Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Petra
authors: P
authors: Schneiderova
authors: Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Regina
authors: R
authors: Fillerova
authors: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Vit
authors: V
authors: Prochazka
authors: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Michaela
authors: M
authors: Mikesova
authors: Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Patrik
authors: P
authors: Flodr
authors: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Karel
authors: K
authors: Indrak
authors: Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic.
authors: Tomas
authors: T
authors: Papajik
mesh_terms: D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C084103:BCL6 protein, human; D051560:Proto-Oncogene Proteins c-bcl-6
keywords: BCL2 rearrangements; BCL6 rearrangements; Complex chromosomal changes; Diffuse large B-cell lymphoma; Non-immunoglobulin gene translocations