Genomic analysis of multiple myeloma using targeted capture sequencing in the Japanese cohort.
Genomic analysis of multiple myeloma using targeted capture sequencing in the Japanese cohort.
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在日本队列中使用靶向捕获测序对多发性骨髓瘤进行基因组分析。
DOI：
10.1111/bjh.16720
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Ogawa S,
中科院分区：
文献类型：
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作者：
Kanamori T;Sanada M;Ri M;Ueno H;Nishijima D;Yasuda T;Tachita T;Narita T;Kusumoto S;Inagaki A;Ishihara R;Murakami Y;Kobayashi N;Shiozawa Y;Yoshida K;Nakagawa MM;Nannya Y;Shiraishi Y;Chiba K;Tanaka H;Miyano S;Horibe K;Handa H;Ogawa S,
以前的基因组研究已经揭示了骨髓瘤细胞的基因组景观。尽管所显示的一些基因组异常被认为与多发性骨髓瘤的分子发病机制和/或临床结果相关，但这些相关性尚未完全理解。本研究的目的是通过靶向捕获测序阐明日本多发性骨髓瘤队列中基因组异常与临床特征之间的相关性。我们分析了154例新发多发性骨髓瘤患者。分析显示，与以前的报道相比，研究队列由频率较低的超二倍体亚型（37.0%）组成，KRAS突变（36.4%）和IGH-CCND 1易位（26.6%）的频率相对较高。此外，我们的靶向捕获测序策略能够检测罕见的IGH相关染色体易位，如IGH-CCND 2和IGH-MAFA。有趣的是，所有10例患者均携带MAX突变，伴有14 q23缺失。del（17 p）患者的临床结局不利，KRAS突变的存在与携带IGH-CCND 1的多发性骨髓瘤患者的生存期较短相关。因此，我们的研究提供了基因组异常的详细情况，这可能对多发性骨髓瘤患者具有潜在的临床应用价值。
Previous genomic studies have revealed the genomic landscape of myeloma cells. Although some of the genomic abnormalities shown are believed to be correlated to the molecular pathogenesis of multiple myeloma and/or clinical outcome, these correlations are not fully understood. The aim of this study is to elucidate the correlation between genomic abnormalities and clinical characteristics by targeted capture sequencing in the Japanese multiple myeloma cohort. We analysed 154 patients with newly diagnosed multiple myeloma. The analysis revealed that the study cohort consisted of a less frequent hyperdiploid subtype (37·0%) with relatively high frequencies ofKRASmutation (36·4%) andIGH‐CCND1translocation (26·6%) compared with previous reports. Moreover, our targeted capture sequencing strategy was able to detect rareIGH‐associated chromosomal translocations, such asIGH‐CCND2andIGH‐MAFA. Interestingly, all 10 patients harbouredMAXmutations accompanied by 14q23 deletion. The patients with del(17p) exhibited an unfavourable clinical outcome, and the presence ofKRASmutation was associated with shorter survival in patients with multiple myeloma, harbouringIGH‐CCND1. Thus, our study provides a detailed landscape of genomic abnormalities, which may have potential clinical application for patients with multiple myeloma.