Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2

• Published in: Blood Vol. 99; no. 4; pp. 1381 - 1387
• Main Authors: Joos, Stefan, Menz, Christiane K., Wrobel, Gunnar, Siebert, Reiner, Gesk, Stefan, Ohl, Sibylle, Mechtersheimer, Gunhild, Trümper, Lorenz, Möller, Peter, Lichter, Peter, Barth, Thomas F.E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-02-2002; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Child; Chromosomes, Human, Pair 2 - genetics; Cluster Analysis; Female; Gene Dosage; Genes, rel - genetics; Hematologic and hematopoietic diseases; Hodgkin Disease - etiology; Hodgkin Disease - genetics; Hodgkin Disease - pathology; Humans; Karyotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph Nodes - metabolism; Lymph Nodes - pathology; Male; Medical sciences; Middle Aged; Nucleic Acid Hybridization - methods; Polymerase Chain Reaction - methods; Polymerase Chain Reaction - standards; Reed-Sternberg Cells - pathology; Chromosomal aberration; Human; Short arm; Copy number; Chromosome A2; Hodgkin disease; Malignant hemopathy; Recurrent; Chromosome 2; Genetic determinism; Characterization; Case study; Gene; Lymphoproliferative syndrome; Cytogenetics; Gain; High malignancy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.4.1381

Hodgkin- and Reed-Sternberg (HRS) cells microdissected from 41 classical Hodgkin lymphomas (cHL) of 40 patients comprising 8 lymphocyte-rich (cHL-LR), 16 nodular sclerosis (cHL-NS), 15 mixed-cellularity (cHL-MC), and 2 lymphocyte-depletion (cHL-LD) subtypes were analyzed by comparative genomic hybridization for recurrently imbalanced chromosomal subregions. Chromosomal gains most frequently involved chromosome 2p (54%), 12q (37%), 17p (27%), 9p and 16p (24% each), and 17q and 20q (20% each), whereas losses primarily affected chromosome 13q (22%). Using fluorescence in situ hybridization, amplification of the REL oncogene was demonstrated within a distinct 2p15-p16 amplicon. The high frequency of 2p overrepresentations including REL, particularly in cHL-NS (88%), suggests that an alternative mechanism of constitutive activation of nuclear factor NF-κB is a hallmark of HRS cells. Hierarchical cluster analysis of chromosomal imbalances revealed a closer relationship among cHL-NS than other subtypes. Furthermore, there is a tendency for different subtypes of cHL-MC tumors characterized by different ages at the time of tumor onset and gain of chromosome 17p. The imbalance pattern of cHL subtypes suggests that different molecular pathways are activated, with REL or other genes on chromosomal band 2p15-p16 playing a fundamental role in the pathogenesis of classical Hodgkin lymphoma.