Detection of recurrent cytogenetic aberrations in multiple myeloma: A comparison between MLPA and iFISH

Abstract

Multiple myeloma (MM) is a genetically heterogeneous disease with diverse clinical characteristics and outcomes. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MM patients. In the present study, MLPA analysis was applied to analyze cytogenetics of CD138 tumor cells of 59 MM samples, and its result was compared, retrospectively, with the interphase fluorescence in situ hybridization (iFISH) data. We firstly established the normal range of each of the 42 diagnostic probes using healthy donor samples. A total of 151 aberrations were detected in 59 patient samples, and 49/59 cases (83.1%) harbored at least one copy number variation. Overall, 0–7 aberrations were detected per case using MLPA, indicating the heterogeneity and complexity of MM cytogenetics. We showed the high efficiency of MLPA and the high congruency of the two methods to assess cytogenetic aberrations. Considering that MLPA analysis is not reliable when the aberration only exits in a small population of tumor cells, it is essential to use both MLPA and iFISH as complementary techniques for the diagnosis of MM.

Low Expression of miR-424-3p is Highly Correlated with Clinical Failure in Prostate Cancer

“…Our study is the first large-scale study investigating the miR-424-3p and CTLA-4 pathway in human prostatectomy specimens (no = 535), we also abled to investigate the correlation to PD1, PD-L1 and subset of T cells. Herein, we found that a low expression of miR-424-3p was significantly correlated to aggressive PC phenotype, worse clinical outcome and reduced time for clinical failure, which is in line with previous in vitro and in vivo studies 36,38,42–46 . We also identified a correlation between miR-424-3p, CTLA-4 and PD-L1, which is in accordance with one previous report 12 .…”

“…Recently, Zhang et al . reported a functional role of miR-424/Akt3/E2F3 axis in hepatocellular carcinoma development, suggesting that miR-424 could be a potential indicator of prognosis 36 . In PC there is only a limited number of studies and they all has limitation mentioned above.…”

Microenvironment drug resistance in multiple myeloma: emerging new players

“…De novo resistance is present before the drug exposure and then selected during the drug treatment [ 3 ]. Recent studies have demonstrated, by inter-phase fluorescence in situ hybridization (iFISH) [ 5 ] and flow cytometry [ 6 ], the heterogeneity of MM cells at genetic (chromosome number, genetic translocations and mutations), clonal and cell differentiation levels. In particular, flow cytometry analysis reveals the presence of multiple cell clones in patients at diagnosis that are selected by in vivo therapeutic pressure and induce a distinct phenotypic MM cell subclone with different clonogenic and cytogenetic profiles in minimal residual disease [ 6 ].…”

Prediction and prognostic significance of BCAR3 expression in patients with multiple myeloma

“…MM is a B cell differentiated tumor characterized by clonal proliferation of tumor cells [1–3]. MM is a heterogeneous disease with different clinical characteristics [4]. By recognizing genetic mechanism and mutation, a normal plasma cell transited into the following disease stages: monoclonal gammopathy of undetermined significance, smouldering myeloma, myeloma and plasma cell leukaemia [5].…”