Genetic aberrations in multiple myeloma characterized by cIg-FISH: a Brazilian context

Genetic abnormalities are critical prognostic factors for patients diagnosed with multiple myeloma (MM). This retrospective, multicenter study aimed to contribute with the genetic and clinical characterization of MM patients in a country with continental dimensions such as Brazil. Genetic abnormalities were assessed by cIg-fluorescent in situ hybridization (cIg-FISH) in a series of 152 MM patients (median age 55 years, 58.5% men). Overall, genetic abnormalities were detected in 52.7% (80/152) of patients. A 14q32 rearrangement was detected in 33.5% (n=51), including t(11;14), t(4;14) and t(14;16) in 18.4, 14.1, and 1% of cases, respectively. del(13q) was identified in 42.7% (n=65) of patients, of whom 49.2% (32/65) presented a concomitant 14q32 rearrangement. del(17p) had a frequency of 5.2% (n=8). del(13q) was associated with high plasma cell burden (≥50%, P=0.02), and del(17p) with advanced ISS stages (P=0.05) and extramedullary disease (P=0.03). t(4;14) was associated with advanced Durie-Salmon stages (P=0.008), renal insufficiency (P=0.01) and was more common in patients over 60 years old. This study reports similar frequencies of genetic abnormalities to most series worldwide, whereas the t(14;16) and del(17p), two high risk factors for newly diagnosed patients, exhibited lower frequencies. Our results expand the knowledge on the molecular features of MM in Brazil, a country where innovative therapies that could overcome a poor prognosis for some genetic abnormalities are not always available.染色体遗传异常是确诊多发性骨髓瘤（multiple myeloma, MM）患者的关键预后影响因素。本项回顾性多中心研究旨在针对巴西这类幅员辽阔的国家，为多发性骨髓瘤患者的遗传与临床特征研究提供数据支持。本研究采用免疫球蛋白荧光原位杂交（cIg-fluorescent in situ hybridization, cIg-FISH）技术，对152例MM患者的遗传异常情况进行检测，该队列患者的中位年龄为55岁，男性占比58.5%。整体而言，52.7%（80/152）的患者检出遗传异常。其中14q32重排的检出率为33.5%（n=51），包含t(11;14)、t(4;14)及t(14;16)三种亚型，其检出率分别为18.4%、14.1%及1.0%。42.7%（n=65）的患者检出13q染色体缺失（del(13q)），其中49.2%（32/65）同时伴随14q32重排。17p染色体缺失（del(17p)）的检出率为5.2%（n=8）。13q染色体缺失与高浆细胞负荷（≥50%，P=0.02）显著相关；17p染色体缺失则与进展期国际分期系统（International Staging System, ISS）分期（P=0.05）及髓外病变（P=0.03）显著相关。t(4;14)与进展期杜尔-萨尔蒙（Durie-Salmon）分期（P=0.008）、肾功能不全（P=0.01）显著相关，且在60岁以上患者中检出率更高。本研究检出的遗传异常总体发生率与全球多数同类研究队列相近，但针对初诊患者的两项高危因素——t(14;16)与17p染色体缺失（del(17p)），其检出率相对更低。本研究结果进一步丰富了巴西人群多发性骨髓瘤的分子特征研究数据；巴西作为幅员辽阔的国家，部分可改善特定遗传异常相关不良预后的创新疗法尚未完全可及。