Marsden Lily, Jennings Lawrence J, Gadd Samantha, Yu Min, Perlman Elizabeth J, Cajaiba Mariana M
Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611.
Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL - 60611.
Hum Pathol. 2017 Feb;60:32-36. doi: 10.1016/j.humpath.2016.09.025. Epub 2016 Oct 18.
Metanephric stromal tumors (MSTs) are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors, along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in MSTs and in other pediatric renal stromal tumors. In this study, 17 MSTs, 22 congenital mesoblastic nephromas, and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing. Tumor genomic DNA was extracted from formalin-fixed paraffin-embedded tissue, followed by polymerase chain reaction amplification and Sanger dideoxy sequencing with primers flanking the BRAF exon 15 gene. BRAF exon 15 mutations were found in 11 (65%) of the 17 cases of MST, all corresponding to a thymidine-to-adenine substitution at codon 600 (BRAF V600E). All other renal stromal tumors tested were negative for BRAF exon 15 mutations. In conclusion, BRAF V600E mutations are encountered in most MSTs, supporting a link with other metanephric tumors and suggesting a clonal event possibly affecting primordial renal cells. In addition, BRAF V600E mutations have been associated with oncogene-induced senescence in other benign tumors, providing clues to the pathogenesis of metanephric neoplasms in keeping with their overall benign behavior. Our results also suggest a potential diagnostic use for BRAF exon 15 mutations in differentiating MSTs from other pediatric renal stromal tumors, particularly in limited samples.
后肾间质肿瘤（MSTs）是一种罕见的肾脏间质肿瘤，主要影响儿童。它与后肾腺纤维瘤和后肾腺瘤同属后肾肿瘤家族。先前有文献报道，88%的后肾腺瘤以及个别后肾腺纤维瘤存在BRAF外显子15突变，这促使我们去研究这些突变在MSTs以及其他儿童肾脏间质肿瘤中的发生率。在本研究中，选取了17例MSTs、22例先天性中胚层肾瘤和6例婴儿期骨化性肾肿瘤进行BRAF外显子15检测。从福尔马林固定石蜡包埋组织中提取肿瘤基因组DNA，随后进行聚合酶链反应扩增，并使用位于BRAF外显子15基因两侧的引物进行桑格双脱氧测序。在17例MSTs病例中的11例（65%）发现了BRAF外显子15突变，均为密码子600处的胸腺嘧啶到腺嘌呤的替换（BRAF V600E）。所有其他检测的肾脏间质肿瘤BRAF外显子15突变均为阴性。总之，大多数MSTs存在BRAF V600E突变，这支持了其与其他后肾肿瘤的联系，并提示这可能是一个影响原始肾细胞的克隆事件。此外，BRAF V600E突变在其他良性肿瘤中与癌基因诱导的衰老有关，这为后肾肿瘤的发病机制提供了线索，与其总体良性行为相符。我们的结果还表明，BRAF外显子15突变在鉴别MSTs与其他儿童肾脏间质肿瘤方面具有潜在的诊断用途，特别是在样本有限的情况下。
