Knezevich S R, Garnett M J, Pysher T J, Beckwith J B, Grundy P E, Sorensen P H
Department of Pathology, British Columbia's Children's Hospital, Vancouver, Canada.
Cancer Res. 1998 Nov 15;58(22):5046-8.
Congenital mesoblastic nephroma (CMN) is an infantile spindle cell tumor of the kidney that is subdivided into "classical" and "cellular" forms based on the degree of cellularity and mitotic activity. The histogenesis of CMN remains obscure, but relationships to other pediatric renal neoplasms have been proposed. However, cellular CMN is virtually identical histologically to congenital fibrosarcoma (CFS), a malignant tumor of fibroblasts in children of the same age group. Moreover, cytogenetic studies have reported common trisomies in CFS and cellular CMN, particularly of chromosome 11. We show here that t(12;15)(p13;q25)-associated ETV6-NTRK3 gene fusions described in CFS are also present in cellular CMN. ETV6-NTRK3 chimeric transcripts were detected in 8 of 9 cellular CMNs and 2 of 2 mixed CMNs. In contrast, all of the four classical CMNs tested were negative, as were cases of Wilms' tumor and clear cell sarcoma of the kidney. Moreover, we found trisomy 11 only in cellular or mixed CMNs with the ETV6-NTRK3 gene fusion. Our studies indicate that classical and cellular CMN have different genetic features and support the concept that cellular CMN is histogenetically related to CFS. They also provide insight into potential mechanisms involved in the transformation of the classical into the cellular form of CMN.
先天性中胚层肾瘤（CMN）是一种婴儿期肾脏的梭形细胞瘤，根据细胞密度和有丝分裂活性可分为“经典型”和“细胞型”。CMN的组织发生仍不清楚，但有人提出了它与其他儿童肾肿瘤的关系。然而，细胞型CMN在组织学上与先天性纤维肉瘤（CFS）几乎相同——CFS是同一年龄组儿童的成纤维细胞恶性肿瘤。此外，细胞遗传学研究报告称，CFS和细胞型CMN存在常见的三体性，尤其是11号染色体。我们在此表明，CFS中描述的与t(12;15)(p13;q25)相关的ETV6-NTRK3基因融合也存在于细胞型CMN中。在9例细胞型CMN中的8例以及2例混合型CMN中的2例中检测到了ETV6-NTRK3嵌合转录本。相比之下，所检测的4例经典型CMN均为阴性，肾母细胞瘤和肾透明细胞肉瘤病例也是如此。此外，我们仅在具有ETV6-NTRK3基因融合的细胞型或混合型CMN中发现了11号染色体三体性。我们的研究表明，经典型和细胞型CMN具有不同的遗传特征，并支持细胞型CMN在组织发生学上与CFS相关的概念。它们还为经典型CMN转变为细胞型CMN的潜在机制提供了见解。
