Identification of recurrent chromosomal breakpoints in multiple myeloma with complex karyotypes by combined G-banding, spectral karyotyping, and fluorescence in situ hybridization analyses.
The description of novel chromosomal aberrations in multiple myeloma (MM) remains necessary to fully understand the pathogenesis of this heterogeneous disease. Therefore, we have used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) with locus-specific probes to characterize the chromosomal abnormalities in 11 MM cases in which G-banding revealed a complex karyotype. SKY refined G-banding karyotypes in all cases. Recurrent breakpoints involved bands Xp11, 8q24, 11q13, 12q13, 13q21, and 14q32. In addition, combined SKY and FISH analyses permitted us to identify a subset of patients harboring 22q11.2 rearrangements not involving the IGL locus. This finding suggests the presence of other gene(s) in band 22q11 that might be implicated in MM pathogenesis. Moreover, band 1p13 was identified as a novel partner of immunoglobulin (IG) translocations in MM. Finally, using interphase FISH, we have detected interstitial deletions in 13q14 and 17p13, as well as cryptic translocations affecting IGH, which were neither detected by G-banding nor by SKY. The results of the present study suggest the existence of hitherto unknown nonrandom chromosomal changes that may play a role in the pathogenesis of MM. Our findings underline the importance of the combination of banding, SKY, and FISH analyses to increase the accuracy of karyotype interpretation in plasma cell neoplasias.
Sáez
Borja
B
Department of Genetics, University of Navarra, Irunlarrea s/n, Pamplona, Navarra 31008, Spain. bsaezoch@alumni.unav.es
Martín-Subero
José I
JI
Largo
Cristina
C
Martín
María C
MC
Odero
María D
MD
Prosper
Felipe
F
Siebert
Reiner
R
Calasanz
María J
MJ
Cigudosa
Juan C
JC
D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002882:Chromosomes, Human, Pair 13; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009101:Multiple Myeloma / Q000235:genetics*; D032681:Spectral Karyotyping
D056741:Cyclin D; D016213:Cyclins