Mikulasova Aneta, Smetana Jan, Wayhelova Marketa, Janyskova Helena, Sandecka Viera, Kufova Zuzana, Almasi Martina, Jarkovsky Jiri, Gregora Evzen, Kessler Petr, Wrobel Marek, Walker Brian A, Wardell Christopher P, Morgan Gareth J, Hajek Roman, Kuglik Petr
Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Department of Medical Genetics, University Hospital Brno, Brno, Czech Republic.
Eur J Haematol. 2016 Dec;97(6):568-575. doi: 10.1111/ejh.12774. Epub 2016 Jun 9.
Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy-number alterations (CNAs) in 90 MGUS and 33 MM patients using high-density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10 ) and showed median number of CNAs is lower in MGUS (3, range 0-22) than in MM (13, range 4-38, P = 1.82 × 10 ). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.
意义未明的单克隆丙种球蛋白病（MGUS）是一种良性疾病，每年有大约1%的风险发展为有症状的浆细胞疾病，主要是多发性骨髓瘤（MM）。我们使用高密度DNA微阵列对90例MGUS患者和33例MM患者进行了全基因组拷贝数改变（CNA）筛查。我们发现MGUS患者中CNA的比例（65.6%）低于MM患者（100.0%，P = 1.31×10），且MGUS患者的CNA中位数（3，范围0 - 22）低于MM患者（13，范围4 - 38，P = 1.82×10）。在MGUS队列中，最常见的缺失位于1p（5.6%）、6q（6.7%）、13q（30.0%）、14q（14.4%）、16q（8.9%）、21q（5.6%），最常见的增益位于1q（23.3%）、2p（6.7%）、6p（13.3%）和Xq（7.8%）。在38.9%的MGUS病例中检测到超二倍体，最常见的全染色体增益是3（25.6%）、5（23.3%）、9（37.8%）、15（23.3%）和19（32.2%）。我们还发现了如1p、6q、8p、12p、13q、16q缺失、1q增益和亚二倍体等CNA，它们可能与MGUS的不良预后相关。总之，我们表明MGUS与MM相似，都是基因异质性疾病，但总体细胞遗传学不稳定性低于MM，这证实了基因异常在单克隆丙种球蛋白病中起重要作用。
