BCL6 alternative breakpoint region break and homozygous deletion of 17q24 in the nodular lymphocyte predominance type of Hodgkin's lymphoma–derived cell line DEV

• Published in: Human pathology Vol. 37; no. 6; pp. 675 - 683
• Main Authors: Atayar, Çiğdem, Kok, Klaas, Kluiver, Joost, Bosga, Anneke, van den Berg, Eva, van der Vlies, Pieter, Blokzijl, Tjasso, Harms, Geert, Davelaar, Inge, Sikkema-Raddatz, Birgit, Martin-Subero, Josẻ Ignacio, Siebert, Reiner, Poppema, Sibrand, van den Berg, Anke
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2006; Elsevier; Elsevier Limited
• Subjects: 17q24 deletion; BCL6 ABR breakpoint; Biological and medical sciences; Cell Line, Tumor; Chromosome Breakage; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 17; Cloning; Cytogenetic Analysis; DEV; DNA-Binding Proteins - genetics; Genetic Markers; Hematologic and hematopoietic diseases; Hodgkin Disease - genetics; Hodgkin Disease - pathology; Hodgkin's lymphoma; Homozygote; Humans; Immunohistochemistry; Immunophenotyping; In Situ Hybridization, Fluorescence; Investigative techniques, diagnostic techniques (general aspects); Kinases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes - physiology; Male; Medical sciences; Microsatellite Repeats; Middle Aged; NLPHL; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Proto-Oncogene Proteins c-bcl-6; Signal transduction; Germany; NLPHL; 17q24 deletion; BCL6 ABR breakpoint; DEV; Hodgkin's lymphoma; Breakpoint; Break; Hodgkin disease; Malignant hemopathy; Homozygosity; Anatomic pathology; Cell line; Chromosome E17; Lymphoproliferative syndrome; C-Onc gene; Established cell line; Deletion; Lymphocyte-predominant Hodgkin lymphoma; Tumor cell; Protooncogene
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2006.01.018

DEV is the only cell line derived from nodular lymphocyte predominance type of Hodgkin's lymphoma (NLPHL); however, a comprehensive report about the genetic and immunophenotypic profile of this unique cell line is lacking. We analyzed DEV with respect to immunophenotype and genetic aberrations. The immunostaining revealed positivity for CD45, CD20, CD22, CD79a, IgA2, CD80, CD86, CD74, and BCL6. Cytogenetically, DEV has complex chromosome 3 translocations involving chromosomes 7, 14, and 22. A detailed analysis of the 3q27 breakpoint of the der(3)t(3;14)(p14;q32)t(3;22)(q27;q11.2) revealed a break in the BCL6 alternative breakpoint region. Using array comparative genomic hybridization, a 3-megabase homozygous deletion at 17q24.1-24.2 was identified. Fluorescence in situ hybridization indicated the presence of 2 chromosome 17 homologues, each of which carried a small interstitial deletion. Eight microsatellite markers flanking the homozygously deleted region all showed a homozygous pattern suggesting loss of one of the parental alleles. D17S1809 and D17S1816 could not be amplified using DEV DNA, in keeping with a location within the homozygously deleted segment. In conclusion, DEV has an immunophenotype that is consistent with the neoplastic cells of NLPHL cases, the lymphocytic and histiocytic cells. We demonstrated involvement of the BCL6 gene based on the presence of a breakpoint in the alternative breakpoint region and nuclear staining for BCL6 protein and identified a homozygously deleted region at 17q24.