Cytogenetic Abnormalities in Multiple Myeloma Patients at a Tertiary Healthcare Center in India

Abstract

Objective: Multiple myeloma (MM) is a clinically and genetically heterogeneous plasma cell neoplasm. The prognosis of MM patients is dependent on several factors including the patient’s age, the stage of disease and genetic alterations. This study aimed to determine the frequency of common chromosomal abnormalities and their significance in MM patients referred to a tertiary healthcare center in India. Methods: Fluorescence in situ hybridization on interphase nuclei from bone marrow cells using seven MM-specific probes for recurrent aberrations was performed in a total of 215 newly diagnosed patients. Results: Chromosomal abnormalities were detected in 161 (74.9%) MM patients in this study. The most frequent aberration was trisomy(ies) involving only gain of chromosomes in 48 (22.3%) cases. A translocation involving the IGH gene alone or accompanied by trisomy(ies) or by monosomy 13/13q deletion or by both was registered in 80 (37.2%) patients. Atypical patterns such as a deletion of the IGH variable segment (IGHv) on the derivative chromosome 14 or on the native (normal) chromosome 14, biallelic deletion of IGHv, deletion of the IGH constant segment on the rearranged chromosome14 and extra fusions were noticed in 21 (9.8%) patients with an IGH rearrangement. Monosomy 13/deletion 13q was identified singly or as part of a complex karyotype in 74 patients (34.4%). Clonal heterogeneity and additional abnormalities including TP53 deletion and monosomies of chromosomes 4, 9, 14 and 16 were recorded in 18.6% and 16.3% of patients respectively. Patients with abnormalities exhibited plasmacytosis, reduced hemoglobin value and high level of ß2-microglobulin. Conclusions: A lower median age and a low frequency of IGH translocations particularly t(11;14) and chromosome 13 abnormalities suggest ethnic diversity. Further investigations on genetic alterations including IGH deletions will contribute to improved insights into the biology of myeloma disease, risk stratification and patient management.

Cytogenetic Alterations and Correlation with Age and Gender in Patients of Multiple Myeloma: A Study from a Tertiary Care Center in Eastern India

“…1 The overall frequency (22.2%) observed in this study was higher than that reported by other studies from Western India (10-15%). 13,14 Deletion 17p is known to acquire during the course of progression of the disease and is more common to occur in relapsed/refractory setting. Lakshman et al 15 reported acquisition of del 17p at a median of 35.6 months of diagnosis after a median of two lines of therapy.…”

“…The various centers observed frequencies ranging from 33.3 to 74.9%. 10 11 12 13 These studies differed in their results as the range of CAs selected for testing was highly variable and so was the method used for cytogenetic study (FISH only/FISH and conventional CG/CG only). The studies that included ploidy level along with immunoglobulin heavy-chain (IgH) translocations reported higher incidence rates of CAs.…”

“…Previous studies from India have also reported lower frequency rates ranging from 25 to 34.4%. 10 13 14 Monosomy 13 imparts unfavorable prognosis in myeloma, probably due to its frequent association with other high-risk CAs, especially t(4;14). In the current study, two-thirds cases of del 13q were seen in association with other CAs; with t(4;14) (22/143), with del 17p (13/143), with del 17p and del 14q (8/143), and with t(11;14) (11/143).…”

“… 1 The overall frequency (22.2%) observed in this study was higher than that reported by other studies from Western India (10–15%). 13 14 …”

A diagnostic approach to detect cytogenetic heterogeneity and its prognostic significance in multiple myeloma

“… 2 Metaphase analysis by G banding provides us with a tool to detect aberrations at the cellular level in 30–50% of patients in advanced stages than in cases with newly diagnosed MM. 3 In patients with a low proliferative index, the identification of cryptic anomalies is better detected by interphase fluorescence in situ hybridization (iFISH) than by conventional cytogenetics (CCs). iFISH is a more sensitive method as this technique can facilitate detection on a cell-by-cell basis using region-specific probes.…”