High prevalence of immunoglobulin light chain gene aberrations as revealed by FISH in multiple myeloma and MGUS

Abstract

Multiple myeloma (MM) is a malignant B-cell neoplasm characterized by an uncontrolled proliferation of aberrant plasma cells in the bone marrow. Chromosome aberrations in MM are complex and represent a hallmark of the disease, involving many chromosomes that are altered both numerically and structurally. Nearly half of the cases are nonhyperdiploid and show IGH translocations with the following partner genes: CCND1, FGFR3 and MMSET, MAF, MAFB, and CCND3. The remaining 50% are grouped into a hyperdiploid group that is characterized by multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21. In this study, we analyzed the immunoglobulin light chain kappa (IGK, 2p12) and lambda (IGL, 22q11) loci in 150 cases, mostly with MM but in a few cases monoclonal gammopathy of undetermined significance (MGUS), without IGH translocations. We identified aberrations in 27% (= 40 patients) including rearrangements (12%), gains (12%), and deletions (4.6%). In 6 of 18 patients with IGK or/and IGL rearrangements, we detected a MYC rearrangement which suggests that MYC is the translocation partner in the majority of these cases.

MYCamplifications in myeloma cell lines: correlation with MYC-inhibitor efficacy

“…Indeed, recent publications indicate that different rearrangements involving MYC cause elevated MYC expression in nearly half of newly diagnosed patients. [ 13 – 15 ] MYC expression has been reported to affect cell proliferation and energy metabolism in rapidly proliferating cancer cells. [ 7 ] Amplification of the MYC gene seen in myeloma cell lines may be a consequence of the selection pressure for proliferation and survival in tissue culture flasks.…”

“…[ 13 , 14 ] Moreover, MYC was shown to be the most frequent translocation partner in aberrations involving the immunoglobulin light chains. [ 15 ] Altogether, MYC rearrangements were found in nearly half of the myeloma patients leaving MYC the most commonly mutated gene in multiple myeloma. [ 13 ]…”

Interphase Fluorescence in Situ Hybridization Analysis of Cytogenetic Abnormalities in Egyptian Patients with Plasma Cell Myeloma

“…While it was much lower than that observed by Fonesca et al (2003) (54.2%) [20] , Zhan et al (2006) (50%) [22] who were studying the role of cytogenetics by FISH and conventional cytogenetics (Karyotyping) in myeloma patients using a larger scale of patients (794 and 1064), Hu et al (2011) (47.2%) [11] and Turkman et al (2014) (44%) [23] .…”

FGFR3 mRNA overexpression defines a subset of oligometastatic colorectal cancers with worse prognosis

“…Sixty tumor cell nuclei were analyzed in each tumor by counting green and orange signals of gene amplification probes. Break apart probes for the detection of rearrangements were evaluated in 50 contiguous tumor cell nuclei where tumors with ≥15% split orange and green signals were considered positive as previously described [ 46 , 47 ]. In 10 cases with insufficient tissue or signal quality we accepted a minimum of 20 evaluable tumor cells.…”