Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors.
The pathogenesis of multiple myeloma (MM) is thought to involve at least two pathways, which generate hyperdiploid (HRD) or nonhyperdiploid (NHRD) tumors, respectively. Apart from chromosome content, the two pathways are distinguished by five primary immunoglobulin heavy chain (IGH) rearrangements (4p16, FGFR3, and MMSET; 6p21, CCND3; 11q13, CCND1; 16q23, MAF; 20q12, MAFB) that are present mainly in NHRD tumors. To determine the prevalence and structures of IGH, immunoglobulin (IG) light chain, and MYC genomic rearrangements in MM, we have done comprehensive metaphase fluorescent in situ hybridization analyses on 48 advanced MM tumors and 47 MM cell lines. As expected, the prevalence of the five primary IGH rearrangements was nearly 70% in NHRD tumors, but only 12% in HRD tumors. However, IGH rearrangements not involving one of the five primary partners, and IG light chain rearrangements, have a similar prevalence in HRD and NHRD tumors. In addition, MYC rearrangements, which are thought to be late progression events that sometimes do not involve an IG heavy or light chain locus, also have a similar prevalence in HRD and NHRD tumors. In contrast to the primary IGH rearrangements, which usually are simple balanced translocations, these other IG rearrangements usually have complex structures, as previously described for MYC rearrangements in MM. We conclude that IG light chain and MYC rearrangements, as well as secondary IGH rearrangements, make similar contributions to the progression of both HRD and NHRD MM tumors.
Gabrea
Ana
A
Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. anagabrea@mail.nih.gov
Martelli
Maria Luisa
ML
Qi
Ying
Y
Roschke
Anna
A
Barlogie
Bart
B
Shaughnessy
John D
JD
Sawyer
Jeffrey R
JR
Kuehl
W Michael
WM
D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D004171:Diploidy; D015321:Gene Rearrangement; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D007147:Immunoglobulin Light Chains