title: Rare double-hit with two translocations involving IGH both, with BCL2 and BCL3, in a monoclonal B-cell lymphoma/leukemia.
abstract: BACKGROUND
  Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disease characterized by multiple recurring clonal cytogenetic anomalies and is the most common leukemia in adults. Chromosomal abnormalities associated with CLL include trisomy 12 and IGH;BCL3 rearrangement [t(14;19)(q32;q13)] that juxtaposes a proto-oncogenic gene BCL3 and an immunoglobulin heavy chain, a translocation that may be associated with shorter survival. In addition to the IGH;BCL3 rearrangement, other translocations involving 14q32 locus are involved in various lymphoproliferative pathologies pointing toward the significance of IGH locus in oncogenic progression. Significantly, in the majority of B-cell neoplasms that carry an IGH;BCL3 rearrangement, it is a sole translocation involving an IGH locus.
  
  
  METHODS
  We report a patient who, in addition to trisomy 12, carried a rare double-hit translocation characterized by the IGH;BCL3 translocation and an additional clonal IGH;BCL2 translocation involving IGH and another proto-oncogene BCL2, t(14;18)(q32;q21), commonly found in follicular lymphoma. Further single nucleotide polymorphism (SNP) array-based analysis detected a duplication of the 58.8 kb region at 19q13.32 adjacent to the BCL3 translocation junction on chromosome 19q13. Interestingly, the duplicated region contained ERCC2 gene, which encodes a DNA excision repair protein involved in the cancer-prone syndrome, xeroderma pigmentosum.
  
  
  CONCLUSIONS
  Taken together our findings indicate the existence of double-translocation driven oncogenic events involving both IGH loci and proto-oncogenes BCL2 and BCL3. Importantly, the IGH;BCL3 translocation was characterized by the duplication of the genomic region adjacent to BCL3, containing a major DNA repair factor, ERCC2.
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Alpatov
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Billie
authors.initials: B
authors.lastname: Carstens
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Harding
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Jarrett
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Sudabeh
authors.initials: S
authors.lastname: Balakhani
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lincoln
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Brzeskiewicz
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Ohene-Mobley
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: LeRoux
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: McDaniel
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Meltesen
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Minka
authors.affiliation: Halifax Medical Specialists PA, Roanoke Rapids, NC USA.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Patel
authors.affiliation: Eastern Carolina Pathology Associates, 1705 Tarboro Street SW, Wilson, NC 27893 USA.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Manavi
authors.affiliation: Colorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, 3055 Roslyn Street, Suite 200, Denver, CO 80238 USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Swisshelm
keywords: B-cell lymphoma/leukemia; Double IGH;BCL2 and IGH;BCL3 translocation; ERCC2 duplication