Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
Internal Medicine V (Hematology & Oncology), Medical University of Innsbruck, Innsbruck, Austria.
Eur J Haematol. 2023 Mar;110(3):296-304. doi: 10.1111/ejh.13905. Epub 2022 Dec 4.
Long-term disease control in multiple myeloma (MM) is typically an unmet medical need, and most patients experience multiple relapses. Fluorescence in situ hybridization (FISH) is the standard technique to detect chromosomal abnormalities (CAs), which are important to estimate the prognosis of MM and the allocation of risk adapted therapies. In advanced stages, the importance of CAs needs further investigation. From 148 MM patients, two or more paired samples, at least one of which was collected at relapse, were analyzed by FISH. Using targeted next-generation sequencing, we molecularly investigated samples harboring relapse-associated CAs. Sixty-one percent of the patients showed a change in the cytogenetic profile during the disease course, including 10% who acquired high-risk cytogenetics. Amp(1q) (≥4 copies of 1q21), driven by an additional increase in copy number in patients who already had 3 copies of 1q21, was the most common acquired CA with 16% affected patients. Tetraploidy, found in 10% of the samples collected at the last time-point, was unstable over the course of the disease and was associated with TP53 lesions. Our results indicate that cytogenetic progression is common in relapsed patients. The relatively high frequency of amp(1q) suggests an active role for this CA in disease progression.
在多发性骨髓瘤（MM）中，长期的疾病控制通常是未满足的医疗需求，大多数患者会经历多次复发。荧光原位杂交（FISH）是检测染色体异常（CAs）的标准技术，这对于估计 MM 的预后和分配风险适应治疗非常重要。在晚期，CAs 的重要性需要进一步研究。对 148 名 MM 患者的两个或更多配对样本进行了 FISH 分析，至少有一个样本是在复发时采集的。通过靶向二代测序，我们对携带复发相关 CA 的样本进行了分子研究。在疾病过程中，61%的患者的细胞遗传学特征发生了变化，其中 10%的患者获得了高危细胞遗传学特征。在已经有 3 个 1q21 拷贝的患者中，由于额外增加了拷贝数，导致 1q21 扩增（Amp(1q)）（≥4 个拷贝），这是最常见的获得性 CA，受影响的患者占 16%。在最后一次采集的样本中，有 10%发现四倍体，在疾病过程中不稳定，与 TP53 损伤有关。我们的研究结果表明，细胞遗传学进展在复发患者中很常见。Amp(1q) 的相对高发率表明该 CA 在疾病进展中具有活跃作用。
