High incidence and intraclonal heterogeneity of chromosome 11 aberrations in patients with newly diagnosed multiple myeloma detected by multiprobe interphase FISH.
In multiple myeloma, additional copies of chromosome 11 material, reported to confer an unfavorable prognosis, have been found in 20-45% of patients. To assess the incidence and extent of chromosome 11 aberrations, we performed interphase fluorescence in situ hybridization on CD138+ bone marrow plasma cells of 50 newly diagnosed myeloma patients, using seven locus-specific probes for chromosome 11, one for 13q14.3, and a probe set for translocation t(11;14). In 33 of 50 patients, chromosome 11 aberrations were found. Results indicated a marked intraclonal heterogeneity: in 13 patients, trisomy 11; in 10 patients, subclones with trisomy 11 and partial trisomies 11q coexisted; in 6 patients, only a partial trisomy 11q; and in 6 patients, a tetrasomy or partial tetrasomy 11. The coexistence of subclones with varying extent and copy numbers of chromosome 11 material indicates ongoing structural changes and clonal evolution. Hybridization results delineated 11q23 and 11q25 as the most frequently gained regions, which supports a relevant pathogenetic role of genes on 11q23 and 11q25. To confirm the high incidence of 11q23 gains, a further 50 patients (total n=100) were analyzed for 11q23 and 13q14.3. Myeloma with gains of 11q23 showed a low frequency of deletion 13q14.3 and may prove to be a distinct subgroup of this disease.
Cremer
Friedrich W
FW
Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany.
Kartal
Mutlu
M
Hose
Dirk
D
Bila
Jelena
J
Buck
Isabelle
I
Bellos
Frauke
F
Raab
Marc-Steffen
MS
Brough
Michaela
M
Moebus
Anke
A
Hager
Hans-Dieter
HD
Goldschmidt
Hartmut
H
Moos
Marion
M
Bartram
Claus R
CR
Jauch
Anna
A
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002999:Clone Cells; D015342:DNA Probes; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D015994:Incidence; D007399:Interphase; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D014178:Translocation, Genetic
D015342:DNA Probes