High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) inpatients with plasma cell malignancies

Citation
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
Citations number
22
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
58
Issue
24
Year of publication
1998
Pages
5640 - 5645
Database
ISI
SICI code
0008-5472(199812)58:24<5640:HIOTTA>2.0.ZU;2-P
Abstract
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.