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Unusual case of leukemic mantle cell lymphoma with amplified CCND1/IGH fusion gene
Author(s) -
GruszkaWestwood Alicja M.,
Atkinson Shayne,
Summersgill Brenda M.,
Shipley Janet,
Elnenaei Manal O.,
Jain Paresh,
Hamoudi Rifat A.,
Kaeda Jaspal S.,
Wotherspoon Andrew C.,
Matutes Estella,
Catovsky Daniel
Publication year - 2002
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1216
Subject(s) - biology , mantle cell lymphoma , cyclin d1 , microbiology and biotechnology , locus (genetics) , fusion gene , genetics , amplicon , cancer research , gene , lymphoma , cell cycle , polymerase chain reaction , immunology
We describe a case of leukemic mantle cell lymphoma (MCL) with complex karyotype and amplification of the CCND1/IGH fusion gene. Testing for the presence of t(11;14), the hallmark of MCL, revealed multiple copies of the fusion signals. We therefore conducted extensive molecular cytogenetic studies to delineate the nature and consequences of such an abnormality. We localized the amplification to the der(14)t(11;14) and to a der(2) chromosome in a form of interspersed chromosome 11 and 14 material. This resulted in high expression of cyclin D1 mRNA and the protein expressed independently of the cell cycle phase. CGH analysis revealed that the overrepresentation on chromosome 11 included chromosomal band 11q23 in addition to the CCND1 locus at 11q13. The band 11q23 harbors the ataxia telangiectasia mutated ( ATM ) gene recently proposed to be involved in the pathogenesis of MCL with high incidence of deletions in this locus. Using YAC 801e11, containing the ATM gene, we demonstrated several hybridization signals, suggesting that this region also formed part of the amplicon. This case also showed TP53 gene abnormalities: protein expression, monoallelic deletion, and a mutation in exon 5. The clinical course was aggressive, and the patient died within 6 months of presentation. This is to our knowledge the first description of amplification of the CCND1/IGH fusion gene in a human neoplasm, which may have played a role in the fulminating course of the disease in this patient. © 2002 Wiley‐Liss, Inc.