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In multiple myeloma, 14q32 translocations are nonrandom chromosomal fusions driving high expression levels of the respective partner genes
Author(s) -
Tian Erming,
Sawyer Jeffrey R.,
Heuck Christoph J.,
Zhang Qing,
Rhee Frits,
Barlogie Bart,
Epstein Joshua
Publication year - 2014
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.22165
Subject(s) - chromosomal translocation , ighv@ , biology , fluorescence in situ hybridization , gene , multiple myeloma , immunoglobulin heavy chain , genetics , cancer research , microbiology and biotechnology , immunology , chromosome , leukemia , chronic lymphocytic leukemia
In studies of patients with multiple myeloma (MM), gene expression profiling (GEP) of myeloma cells demonstrates substantially higher expression of MMSET , FGFR3 , CCND3 , CCND1 , MAF , and MAFB —the partner genes of 14q32 translocations—than GEP of plasma cells from healthy individuals. Interphase fluorescent in situ hybridization (FISH) was used to discriminate between chromosomal translocations involving different regions of the immunoglobulin heavy chain ( IGH ) genes at 14q32. With special probes designed for the constant region ( IGHC ) and the variable region ( IGHV ), IGH translocations were shown to be definite, nonrandom chromosomal fusions of IGHC with the loci of FGFR3, CCND1, CCND3, MAF , and MAFB genes; and IGHV with the locus of MMSET gene. When correlated with GEP results, the IGH translocations were found to drive expression levels of the partner genes to significantly higher levels (spikes) than copy‐number variations. Hence, 42% of IGH translocations were identified among newly diagnosed MM patients (448/1,060). As GEP has become essential for assessing cancer risk, this novel approach is highly consistent with the cytogenetic features of the chromosomal translocations to effectively stratify molecular subgroups of MM on the basis of gene expression profiles of the IGH translocation partner genes in myeloma cells. © 2014 Wiley Periodicals, Inc.