Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes

Abstract

Ependymoblastoma (EBL) and embryonal tumor with abundant neuropil and true rosettes (ETANTR) are very aggressive embryonal neoplasms characterized by the presence of ependymoblastic multilayered rosettes typically occurring in children below 6 years of age. It has not been established whether these two tumors really comprise distinct entities. Earlier, using array-CGH, we identified a unique focal amplification at 19q13.42 in a case of ETANTR. In the present study, we investigated this locus by fluorescence in situ hybridization in 41 tumors, which had morphologically been diagnosed as EBL or ETANTR. Strikingly, FISH analysis revealed 19q13.42 amplifications in 37/40 samples (93%). Among tumors harboring the amplification, 19 samples were identified as ETANTR and 18 as EBL. The three remaining tumors showed a polysomy of chromosome 19. Analysis of recurrent/metastatic tumors (n = 7) showed that the proportion of nuclei carrying the amplification was increased (up to 80-100% of nuclei) in comparison to the corresponding primary tumors. In conclusion, we have identified a hallmark cytogenetic aberration occurring in virtually all embryonal brain tumors with ependymoblastic rosettes suggesting that ETANTR and EBL comprise a single biological entity. FISH analysis of the 19q13.42 locus is a very promising diagnostic tool to identify a subset of primitive neuroectodermal tumors with distinct morphology, biology, and clinical behavior.

Embryonal tumor with abundant neuropil and true rosettes in the brainstem: case report

“…1 In the remaining 10 cases, tumor surgery was attempted, resulting in tumor biopsy in 5 cases 6 and subtotal or gross-total resection in 5 cases. 4,5,7,10 The median survival in the 11 reported cases of brainstem ETANTR was 10.2 months-16.4 months in cases in which subtotal or gross-total resection was achieved, but only 4.0 months in the biopsy and inoperative cases. Kaplan-Meyer survival curves stratified with regard to the extent of resection for the 10 cases with available survival data are shown in Fig.…”

Molecular methods in diagnosis of poorly differentiated malignant brain tumors in children

“…В настоящей работе мы сосредоточились на ре-троспективном исследовании наиболее злокаче-ственных типов опухолей ЦНС у детей (ПНЭО ЦНС, ETMR, АТРО и ГБМ), средняя общая выжи-ваемость при которых не превышает 2 лет и состав-ляет для АТРО 9 мес [16], для ETMR 12 мес [29], для ПНЭО ЦНС 16 мес [21], для ГБМ 24 мес [26].…”

MRI Characteristics of Ependymoblastoma: Results from 22 Centrally Reviewed Cases

“…Recent molecular studies further clearly demonstrate that tumors diagnosed as EBL, ETANTR, or embryonal tumors with multilayered rosettes carry identical, highly specific chromosomal alterations (amplification at 19q and/or gain of chromosome 2). 33 EBL and the proposed "novel" entities therefore represent a single embryonal tumor entity (defined as EBL according to the 2007 World Health Organization classification). 1,12,33,34 Consequently, all 22 tumors of our case collection were designated EBL by central neuropathologic review (T.P.).…”

“…33 EBL and the proposed "novel" entities therefore represent a single embryonal tumor entity (defined as EBL according to the 2007 World Health Organization classification). 1,12,33,34 Consequently, all 22 tumors of our case collection were designated EBL by central neuropathologic review (T.P.). We intend to contribute to this ongoing discussion with the first systematic analysis of imaging characteristics of EBL.…”