Soft tissue tumors of infancy encompass an overlapping spectrum of diseases that pose unique diagnostic and clinical challenges. We studied genomes and transcriptomes of cryptogenic congenital mesoblastic nephroma (CMN), and extended our findings to five anatomically or histologically related soft tissue tumors: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumor, malignant rhabdoid tumor, and clear cell sarcoma of the kidney. A key finding is recurrent mutation of EGFR in CMN by internal tandem duplication of the kinase domain, thus delineating CMN from other childhood renal tumors. Furthermore, we identify BRAF intragenic rearrangements in CMN and IFS. Collectively these findings reveal novel diagnostic markers and therapeutic strategies and highlight a prominent role of isolated intragenic rearrangements as drivers of infant tumors.

中文翻译：

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婴儿软组织肿瘤中EGFR和BRAF的反复基因内重排。

婴儿期的软组织肿瘤涵盖了一系列重叠的疾病，这些疾病构成了独特的诊断和临床挑战。我们研究了隐源性先天性中胚层性肾瘤（CMN）的基因组和转录组，并将我们的发现扩展到五个与解剖或组织学相关的软组织肿瘤：婴儿纤维肉瘤（IFS），成纤维细胞瘤病，威尔姆斯瘤，恶性横纹肌瘤和肾脏的透明细胞肉瘤。一个关键发现是通过激酶域的内部串联重复，CMN中EGFR的复发突变，从而将CMN与其他儿童期肾脏肿瘤区分开来。此外，我们确定在CMN和IFS中的BRAF基因内重排。这些发现共同揭示了新颖的诊断标记和治疗策略，并突出了孤立的基因内重排作为婴儿肿瘤驱动因素的突出作用。