Taniwaki Masafumi
Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science.
Rinsho Ketsueki. 2015 Oct;56(10):2056-65. doi: 10.11406/rinketsu.56.2056.
Specific chromosomal abnormalities are of diagnostic and prognostic relevance as well as providing clues for the identification of causative genes in patients with hematological malignancies. Genomic array (GA) is a powerful tool for identifying both microdeletion and precise DNA breakpoints in the genes of interest. For example, GA was able to detect CDKN2A and CDKN2B deletions in a small region only 69kb in size at 9p21 that were frequently found in patients with double-hit lymphoma. Using GA combined with spectral karyotyping, fluorescence in situ hybridization, and RT-PCR, we have identified a novel PVT1 rearrangement at 8q24 which were partnered with NBEA and WWOX in multiple myeloma (MM). In patients with MM, NBEA and WWOX are frequently involved in chromosomal deletion at 13q14 and 16q23, respectively. In acute myeloid leukemia, novel fusion RNAs, PVT1-NSMCE2 and CCDC26-NSMCE2, were identified in association with marker chromosomes and double minute chromosomes derived from chromosome 8 showing 8q24 amplicons. Chromothripsis is a possible cytogenetic mechanism of generating PVT1-NSMCE2 and CCDC26-NSMCE2. As PVT1 and CCDC26 are long intergenic non-coding RNAs (lincRNAs), our study suggests that the fusion genes involving lincRNAs potentially play as-yet-unknown oncogenic functional roles. Advancements in molecular cytogenetic techniques along with next generation sequencing will facilitate the understanding of tumorigenesis in hematological malignancies.
特定的染色体异常具有诊断和预后相关性，同时也为识别血液系统恶性肿瘤患者的致病基因提供线索。基因组阵列（GA）是识别感兴趣基因中的微缺失和精确DNA断点的有力工具。例如，GA能够检测到9p21上一个仅69kb大小的小区域内的CDKN2A和CDKN2B缺失，这种缺失在双打击淋巴瘤患者中经常出现。通过将GA与光谱核型分析、荧光原位杂交和逆转录聚合酶链反应相结合，我们在8q24发现了一种新的PVT1重排，在多发性骨髓瘤（MM）中它与NBEA和WWOX相关。在MM患者中，NBEA和WWOX分别经常参与13q14和16q23的染色体缺失。在急性髓系白血病中，发现了新的融合RNA，即PVT1-NSMCE2和CCDC26-NSMCE2，它们与源自8号染色体的标记染色体和双微体染色体相关，这些染色体显示8q24扩增子。染色体碎裂是产生PVT1-NSMCE2和CCDC26-NSMCE2的一种可能的细胞遗传学机制。由于PVT1和CCDC26是长链基因间非编码RNA（lincRNA），我们的研究表明涉及lincRNA的融合基因可能发挥尚未明确的致癌功能作用。分子细胞遗传学技术的进步以及下一代测序将有助于理解血液系统恶性肿瘤的肿瘤发生机制。
