Abstract 4702: Chromosome 2p gain and N-Myc amplification predict poor outcome of patients with LIN28 negative supratentorial primitive neuroectodermal tumors of the central nervous system (CNS-PNET)..
Authors: Gessi Marco , von Bueren Andre' , Treszl Andras , zur Muehlen Anja , Rutkowski Stefan , Pietsch Torsten 
Published: August 2014

Primitive neuroectodermal tumors of central nervous system (CNS-PNET) which represents 3-7% of all pediatric brain tumors, are a rare group of neoplasms occurring in the CNS and include supratentorial PNETs (s-PNET), medulloepitheliomas and ependymoblastomas. Whereas ependymoblastomas harbour chromosome 19q13.41 amplification, express the neural stem cell marker LIN28 and show aggressive clinical behaviour, the biological mechanisms and molecular alterations contributing to the pathogenesis of s-PNETs remain so far poorly understood. Expression analyses and limited CGH studies indicated that s-PNETs may represent genetically a heterogeneous group with frequent but multiple copy number aberrations. In order to find possible specific molecular and cytogenetic alterations suitable for molecular risk stratification and predictive for the overall survival, we performed a multiplex ligation-dependent probe amplification (MLPA) and molecular inversion probe (MIP) analysis on DNA samples of 25 s-PNET cases of patients (median age 5.35 years; range, 2.41 - 17.28 years). The majority of patients were enrolled in the clinical GPOH HIT2000 trial. MLPA and MIP analysis revealed large losses of genomic material of chromosomes 3, 4, 5, 13, while frequent gains were observed at chromosomes 1, 17, 19, 20 and 22. Recurrent regions of gains were found at chromosome 7q11.2, 7q22.1, 12q13 and losses at 16q23.1, 6p21.1, and 11q11. High-copy number gains (amplifications) were found in particular at chromosome 2p24.3 (N-Myc) (in 6 cases) and 4q21 (in 2 cases). None of the chromosomal alterations identified was found significantly associated with the age of the patients at diagnosis, presence of tumor metastases or presence of postoperative residual tumor. In contrast, patients with tumors harbouring 2p gain or N-Myc amplification showed shorter overall survival (OS) (p=0.0029 and p=0.0012, respectively).These parameters were independent from the presence of metastases, which was indeed the most important clinical factor for unfavourable OS (p=0.0112) in our series. In the era of the personalized neuro-oncology, the identification of molecular marker associated to patients outcome may represent the further significant step towards the patients's risk stratification and the improvement of therapeutic strategies also for patients suffering from s-PNETs.

Citation Format: Marco Gessi, Andre' von Bueren, Andras Treszl, Anja zur Muehlen, Stefan Rutkowski, Torsten Pietsch. Chromosome 2p gain and N-Myc amplification predict poor outcome of patients with LIN28 negative supratentorial primitive neuroectodermal tumors of the central nervous system (CNS-PNET). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4702. doi:10.1158/1538-7445.AM2013-4702