T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1, TRA-SALL2, and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates >3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1, which predicted a poor prognosis in the adult group. Up-regulation of HOXA, MEF2C, and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.

中文翻译：

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T细胞急性淋巴细胞白血病融合基因的鉴定和转录组特征的表征。

T细胞急性淋巴细胞白血病（T-ALL）是未成熟T细胞的克隆性恶性肿瘤。最近，下一代测序方法已允许系统识别儿科T-ALL中的分子特征。在这里，通过进行RNA测序和其他全基因组分析，我们调查了61名成人和69名儿童T-ALL病例的基因组格局。确定了36种不同的基因融合转录本，其中SET-NUP214与成年病例高度相关。在18个以前未知的融合中，ZBTB16-ABL1，TRA-SALL2和NKX2-1参与是复发事件。ZBTB16-ABL1起到促白血病的作用，并响应酪氨酸激酶抑制剂的作用。在48个突变率> 3％的基因中，有6个是在T-ALL中新发现的。在大多数情况下，TAL1过度表达SLC17A9基因的短mRNA转录异常表达，这预示了成年组的预后不良。上调HOXA，MEF2C和LYL1经常出现在成人病例，而TAL1过表达主要在儿科组中检测到。尽管大多数基因融合是互斥的，但它们却与基因突变共存。这些遗传异常与三个亚组中基因表达标记的失调相关。这项研究可能会进一步丰富当前的T-ALL分子发病机理的知识。