Translocations of 14q32 and deletions of 13q14 are common chromosomal abnormalities in systemic amyloidosis

Abstract

Summary. Systemic monoclonal immunoglobulin light chain amyloidosis (AL) is associated with clonal plasma cell dyscrasias that are often subtle and non-proliferating. AL shares numerical chromosomal changes with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Illegitimate translocations involving the immunoglobulin heavy chain gene (IGH) at 14q32 and deletions of the long arm of chromosome 13, [del(13q)], commonly occur in MM, MGUS and plasma cell leukaemia. In AL IGH rearrangements have been identified but, to date, there are no reports of del(13q). In this study of 32 patients with AL, 24 with systemic and eight with localized disease, translocations involving IGH and del(13q) were found using dual-colour interphase fluorescence in situ hybridization (FISH). IGH translocations were observed in 11 patients (37% overall and in 46% with systemic disease), of which nine had the IGH/CCND1 fusion from t(11;14)(q13;q32). Two showed IGH translocations other than the t(11;14) or t(4;14)(p16;q32). In one of these patients a breakpoint within the constant region of IGH between Ca1 and Ca2 was indicated. In the second a deletion covering Ca1 and Ca2 accompanied the translocation. Ten patients (27% overall and 33% of those with systemic disease) showed del(13q). The gain or loss of IGH and CCND1 signals provided evidence of numerical chromosomal changes in three patients.

Translocation t(11;14) and survival of patients with light chain (AL) amyloidosis

“…The importance of this finding is mitigated by the retrospective nature of the study, which may introduce unintended bias; however, this observation is novel, and should be investigated in a larger, prospectively collected cohort for confirmation. Our cytogenetic findings in AL are similar to those previously published [4][5][6]15,16 (Table 3). Some of the minor differences in results between studies may be explained by different techniques and scoring methodologies used.…”

“…Ten of 32 patients had del13/del3q, and 11 had 14q32 translocation, of whom nine had t (11;14). 6 No patient had t (4;14). Five of the patients with del13/del3q had a concomitant IgH translocation, of whom three had t (11;14).…”

Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis

“…Despite the fact that knowledge about the biology of MM PCs has greatly increased in recent years, 1 the same does not apply to AL. Thus, the cytogenetic profile of patients with AL has only been reported in a few studies [2][3][4][5][6][7] that investigated a limited number of alterations (eg, IGH translocations or 13q and 17p deletion). Apparently, t (11;14) is the most frequent cytogenetic alteration in AL and confers a poor outcome, 4,8 whereas MM-related high-risk cytogenetic abnormalities (ie, [t(4;14), t (14;16) and/or del(17p)]) are prognostically neutral in AL.…”

The enigmatic role of cyclin D1 in multiple myeloma

“…39 By contrast, in MGUS and AL, the proportion of abnormal plasma cells within the S fraction is comparable to the one of normal plasma cells, and translocations involving the IgH locus are frequent, notably the t(11;14)(q13;q32). [40][41][42] The t(11;14)(q13;q32) occurs in 15-20% of MM cells; however, cyclin D1 is detected in 40-50% of cases with various techniques including the highly sensitive real-time quantitative RT-PCR (Table III). [31][32][33][43][44][45] In the absence of t(11;14)(q13;q32), the only chromosomal abnormality associated with cyclin D1 expression is a polysomy of chromosome 11.…”

“…[40][41][42] The t(11;14)(q13;q32) occurs in 15-20% of MM cells; however, cyclin D1 is detected in 40-50% of cases with various techniques including the highly sensitive real-time quantitative RT-PCR…”