Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, University of Wuerzburg, 97074, Wuerzburg, Germany.
Kiel Pediatric Tumor Registry, Section of Pediatric Pathology, Department of Pathology, Christian Albrechts University, 24105, Kiel, Germany.
Nat Commun. 2018 Jun 18;9(1):2378. doi: 10.1038/s41467-018-04650-6.
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.
婴儿软组织肿瘤包含一系列重叠的疾病，这些疾病具有独特的诊断和临床挑战。我们研究了隐匿性先天性中胚层肾瘤 (CMN) 的基因组和转录组，并将我们的发现扩展到五个解剖学或组织学上相关的软组织肿瘤：婴儿纤维肉瘤 (IFS)、肾胚瘤病、Wilms 瘤、恶性横纹肌样瘤和肾透明细胞肉瘤。一个关键的发现是 CMN 中 EGFR 的激酶结构域内串联重复导致的反复突变，从而将 CMN 与其他儿童肾肿瘤区分开来。此外，我们还在 CMN 和 IFS 中发现了 BRAF 基因内重排。这些发现共同揭示了新的诊断标志物和治疗策略，并强调了孤立基因内重排在婴儿肿瘤中的驱动作用。
