Heterogeneous pattern of chromosomal breakpoints involving the MYC locus in multiple myeloma.
Chromosomal rearrangements of the MYC locus, which often involve the IG loci, are recurrent events in multiple myeloma (MM) and plasma cell leukemia (PCL). We used dual-color fluorescence in situ hybridization (FISH) to characterize the breakpoint locations of chromosomal translocations/rearrangements involving the MYC locus at 8q24 found in a panel of 14 MM cell lines and 70 primary tumors (66 MM and 4 PCL). MYC locus alterations were observed in 21 cases: MYC/IG (mainly IGH@) fusions in 11 cell lines and three patients (2 MM and 1 PCL), and extra signals and/or abnormal MYC localizations in seven patients (5 MM and 2 PCL). Fourteen of these cases were investigated by FISH analyses by use of a panel of BAC clones covering about 6 Mb encompassing the MYC locus. The breakpoints were localized in a region 100-250 kb centromeric to MYC in four cases, a region 500-800 kb telomeric to the gene in four cases, and regions > or = 2 Mb centromeric or telomeric to MYC in five cases. Two different breakpoints were detected in the KMS-18 cell line, whereas the insertion of a MYC allele was found in a complex t(16;22) chromosomal translocation in the RPMI8226 cell line. Our data document a relatively high dispersion of 8q24 breakpoints in MM.
Fabris
Sonia
S
Laboratorio di Ematologia Sperimentale e Genetica Molecolare, U.O. Ematologia 1, Dipartimento di Scienze Mediche, Università degli Studi di Milano, Ospedale Maggiore IRCCS, Italy.
Storlazzi
Clelia Tiziana
CT
Baldini
Luca
L
Nobili
Lucia
L
Lombardi
Luigia
L
Maiolo
Anna Teresa
AT
Rocchi
Mariano
M
Neri
Antonino
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002461:Cell Line, Transformed; D019457:Chromosome Breakage / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D016259:Genes, myc / Q000235:genetics*; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D005819:Genetic Markers; D015514:Oncogene Proteins, Fusion