脂肪肉瘤中低分化和高分化成分的早期分离和平行克隆选择

IF 4.8 2区医学 Q1 Biochemistry, Genetics and Molecular Biology

Neoplasia Pub Date : 2024-11-25 DOI:10.1016/j.neo.2024.101074

Tetsuya Sekita , Naofumi Asano , Takashi Kubo , Hirohiko Totsuka , Sachiyo Mitani , Naoko Hattori , Akihiko Yoshida , Eisuke Kobayashi , Motokiyo Komiyama , Toshikazu Ushijima , Robert Nakayama , Masaya Nakamura , Akira Kawai , Hitoshi Ichikawa

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引用次数: 0

摘要

低分化脂肪肉瘤（DDLPS）由高级别低分化（DD）成分和并列的高分化（WD）成分组成。DD 成分被认为是通过获得额外的基因组改变而起源于 WD 成分。在本研究中，我们对三名 DDLPS 患者进行了多区域基因组、表观基因组和转录组分析。在两名患者的所有样本中，几乎没有共同的基因组改变，但在DD或WD成分样本中有许多共同的改变。根据基因组改变预测的系统发生树与根据DNA甲基化模式预测的系统发生树一致。脂肪生成相关基因的表达模式在 DD 和 WD 组份之间存在差异，在不同患者之间也存在差异，这与他们的 CpG 岛甲基化状态有关。这些结果表明，在一些患者中，WD 和 DD 成分在肿瘤发生的早期阶段就已经进化分离，并经过相对较长的克隆选择，获得不同的驱动基因组改变和 DNA 甲基化改变而形成。

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Early separation and parallel clonal selection of dedifferentiated and well-differentiated components in dedifferentiated liposarcoma

Dedifferentiated liposarcoma (DDLPS) comprises a high-grade dedifferentiated (DD) component and a juxtaposed well-differentiated (WD) component. The DD component is believed to originate from the WD component by acquiring additional genomic alterations. In this study, we performed multiregion genome, epigenome, and transcriptome analyses of three patients with DDLPS. In two patients, there were few common genomic alterations across all samples, but many common alterations within DD or WD component samples. Phylogenetic trees predicted from the genomic alterations were consistent with those predicted from DNA methylation patterns. The expression patterns of adipogenesis-related genes differed between DD and WD components and also among patients in connection with their CpG island methylation status. These results indicate that in some patients, WD and DD components are evolutionarily separated at very early stages of tumorigenesis, and are formed through relatively long clonal selection with acquisition of different driver genomic alterations and DNA methylation changes.

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来源期刊

Neoplasia 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

26 days

期刊介绍： Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.