H. Avet-loiseau et al., High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) inpatients with plasma cell malignancies, CANCER RES, 58(24), 1998, pp. 5640-5645
Abnormalities involving the 14q32 region are recurrent chromosomal changes
in plasma cell malignancies. Recent preliminary molecular analyses found IG
H rearrangements in almost 100% of human myeloma cell lines and in 75% of p
atients. Ho However, no systematic study analyzing the nature of the partne
r chromosomal regions have been reported thus far. To define the exact inci
dence of illegitimate IGH rearrangements and the respective incidence of pa
rtner genes cloned to date, we analyzed 141 patients with either multiple m
yeloma (MM, n = 127) or primary plasma cell leukemia (PCL, n = 14) using fl
uorescence in situ hybridization. The overall incidence of illegitimate rec
ombinations was 57% (80 of 141 patients). Analysis of this incidence accord
ing to Durie and Salmon stage, patients' status, i.e., MM versus primary PC
L and diagnosis versus relapse, immunoglobulin type and subtype, and beta 2
-microglobulin value, did not show any correlation. To analyze the nature o
f the partner chromosomal region, we selected probes specific for the follo
wing genes: FGFR3 (4p16), MYC (8q24), CCND1 (11q13), MAF (16q23), and BCL2
(18q21), These probes, combined with differentially labeled 14q32 probes, w
ere used for dual-color fluorescence in situ hybridization on interphase pl
asma cells. Among the 80 patients with illegitimate IGH rearrangement, we i
dentified 23 IGH-CCND1 fusion cases [i.e., t(11;14)], 17 IGH-FGFR3 fusion c
ases [i.e., t(4;14)], 3 IGH-MYC fusion cases [i.e., t(8;14)], and only one
IGH-MAF fusion case. No IGH-BCL2 fusion case was detected,In 37 of 80 patie
nts, none of these partner genes was involved. Analysis of cases with speci
fic translocations according to their bioclinical features at diagnosis did
not show any correlation, This study demonstrated that CCND1 and FGFR3 gen
es are involved together in about 50% of MM and primary PCL patients with i
llegitimate IGH rearrangements.