Multiple myeloma is a clonal malignancy of plasma cells in the bone marrow. Risk stratification is partly based on cytogenetic findings that include abnormalities of the IGH locus as determined by fluorescence in situ hybridization (FISH), such as rearrangements that result in either standard‐risk or high‐risk gene fusions. IGH deletions have been evaluated as a group in multiple myeloma patients with respect to cumulative outcomes but have provided limited guidance. Whether these deletions have the potential to result in gene fusions and thus further stratify patients is unknown. We identified 229 IGH deletions in patients referred for plasma cell dyscrasia genetic testing over 5.5 years. Follow‐up was conducted on 208 of the deletions with dual fusion FISH probes for standard‐risk (IGH ‐CCND1 ) and high‐risk IGH gene fusions (IGH ‐FGFR3 , IGH ‐MAF , IGH ‐MAFB ). Of all deletions identified with follow‐up, 44 (21%) resulted in a gene fusion as detected by FISH, 15 (7%) of which were fusion partners associated with high‐risk multiple myeloma. All fusion‐positive 3′‐IGH deletions (6 fusions) resulted in high‐risk IGH ‐FGFR3 fusions. Of the 15 high‐risk fusion‐positive cases, eight were without other high‐risk cytogenetic findings. This study is the first to evaluate the presence of IGH gene fusions upon identification of IGH deletions and to characterize the deletion locus. Importantly, these findings indicate that follow‐up FISH studies with dual fusion probes should be standard of care when IGH deletions are identified in multiple myeloma.

中文翻译：

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多发性骨髓瘤中的高风险细胞遗传学：进一步检查 IGH 基因区域内的缺失可增强风险分层。

多发性骨髓瘤是骨髓中浆细胞的克隆性恶性肿瘤。风险分层部分基于细胞遗传学发现，包括荧光原位杂交 (FISH) 确定的IGH基因座异常，例如导致标准风险或高风险基因融合的重排。IGH缺失已在多发性骨髓瘤患者的累积结果方面作为一组进行评估，但提供的指导有限。这些缺失是否有可能导致基因融合，从而进一步对患者进行分层尚不清楚。我们确定了 229 IGH5.5 年以上转诊进行浆细胞恶液质基因检测的患者的缺失。对 208 个缺失进行了双融合 FISH 探针的标准风险（IGH - CCND1）和高风险IGH基因融合（IGH - FGFR3、IGH - MAF、IGH - MAFB）的随访。在随访中发现的所有缺失中，44 个（21%）导致 FISH 检测到的基因融合，其中 15 个（7%）是与高危多发性骨髓瘤相关的融合伴侣。所有融合阳性 3'- IGH缺失（6 个融合）导致高危IGH - FGFR3融合。在 15 例高危融合阳性病例中，8 例没有其他高危细胞遗传学发现。这项研究是第一个在鉴定IGH缺失后评估IGH基因融合的存在并表征缺失位点的研究。重要的是，这些发现表明，当在多发性骨髓瘤中发现IGH缺失时，使用双融合探针进行后续 FISH 研究应该是标准护理。