Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes

• DOI: 10.1007/s00401-008-0467-y
• Publication Date: 2008-12-04T05:39:33Z
• Authors: Stefan Pfister; Marc Remke; Mirco Castoldi; Alfa H. C. Bai; Martina U. Mucken...; Andreas Kulozik; Andreas von Deimling; Armin Pscherer; Peter Lichter; Andrey Korshunov
• Keywords: Comparative Genomic Hybridization; Gene Expression Profiling; Gene Amplification; Neoplasms, Germ Cell and Embryonal; Microarray Analysis; Immunohistochemistry; Polymerase Chain Reaction; MicroRNAs; 03 medical and health sciences; 0302 clinical medicine; Child, Preschool; Humans; Female; RNA, Messenger; Cerebellar Neoplasms; Chromosomes, Human, Pair 19; In Situ Hybridization, Fluorescence

Embryonal tumors with abundant neuropil and true rosettes (ETANTR) comprise a rare variant of embryonal brain tumors usually occurring in infants. Only 13 cases have been reported in the literature to date and little is known about the molecular pathogenesis of these tumors. Here, we describe a case of ETANTR in a 2-year-old girl presenting with a large tumor in the vermis of the cerebellum. Histological examination showed clusters of small-undifferentiated cells including ependymoblastic-like rosettes admixed with large fibrillar and paucicellular neuropil-like areas indicative for ETANTR. Genomic imbalances were detected by using array-based comparative genomic hybridization. In addition to trisomy of chromosome 2, which has been previously described in ETANTR, array-CGH revealed high-level genomic amplification of 0.89 Mb at chromosome band 19q13.42 covering a microRNA cluster and several protein-coding genes. This aberration has not been described in any other brain tumor to date, indicating a specific aberration in ETANTR. MicroRNAs contained in the microRNA cluster at 19q13.42 including oncomirs miRNA-372 and miRNA-373 were highly up-regulated in the tumor when compared to normal cerebellum or whole brain. In summary, this is the first report on a potentially specific genetic aberration in ETANTR, supporting the hypothesis of a distinct tumor entity.