TY - JOUR
T1 - ETMR-06. Molecular and clinical characteristics of CNS tumors with BCOR(L1 ) fusion/internal tandem duplication
AU - Gojo, Johannes
AU - Schmitt-Hoffner, Felix
AU - Mauermann, Monika
AU - von Hoff, Katja
AU - Sill, Martin
AU - Korshunov, Andrey
AU - Stichel, Damian
AU - Capper, David
AU - Tauziede-Espariat, Arnault
AU - Varlet, Pascale
AU - Aldape, Kenneth
AU - Abdullaev, Zied
AU - Donson, Andrew
AU - Pahnke, Jens
AU - Schüller, Ulrich
AU - Tran, Ivy
AU - Galbraith, Kristyn
AU - Snuderl, Matija
AU - Alexandrescu, Sanda
AU - Brandner, Sebastian
AU - Łastowska, Maria
AU - Miele, Evelina
AU - Lugt, Jasper v
AU - Meijer, Lisethe
AU - Bunt, Jens
AU - Kramm, Christof
AU - Hansford, Jordan R
AU - Krskova, Lenka
AU - Zapotocky, Michal
AU - Nobusawa, Sumihito
AU - Solomon, David
AU - Haberler, Christine
AU - Jones, Barbara
AU - Sturm, Dominik
AU - Sahm, Felix
AU - Jäger, Natalie
AU - Pfister, Stefan M
AU - Kool, Marcel
PY - 2022/3
Y1 - 2022/3
N2 - Central nervous system (CNS) tumor with BCOR internal tandem duplication (BCOR-ITD) have recently been introduced in the 5th edition of the WHO classification of CNS tumors, however, their molecular makeup and clinical characteristics remain widely enigmatic. This is further complicated by the recent discovery of tumors characterized by gene fusions involving BCOR or its homologue BCORL1. We identified a cohort of 206 BCOR altered CNS tumors via DNA methylation profiling and conducted in-depth molecular and clinical characterization in an international effort. By performing t-SNE clustering analysis we found that BCOR-fusion tumors form a distinct cluster (n=61), adjacent to BCOR-ITD cases (n=145). The identified fusion partners of BCOR(L1) included EP300 (n=20), CREBBP (n=5), and NUTM2HP (n=1). Notably, three cases within the BCOR-ITD cluster harbored a c-terminal intragenic deletion within BCOR. With respect to clinical characteristics gender ratio was balanced in BCOR-fusion cases (m/f, 1.1), whereas predominance of male patients was observed in the BCOR-ITD group (m/f, 1.5). Moreover, age at diagnosis of BCOR-fusion patients was higher as compared to BCOR-ITD cases (15 vs 4.5 years). Interestingly, BCOR-fusion tumors were exclusively found in the supratentorial region being originally diagnosed as ependymomas or gliomas whereas BCOR-ITD emerged across the entire CNS with diverse original diagnoses. 8% of BCOR-ITD and none of BCOR-fusion cases were disseminated at diagnosis. In line with this observation, 40% of first relapses within the BCOR-ITD group were metastatic which was less frequent in BCOR-fusion tumors. Survival estimates demonstrated no differences, generally showing short median PFS (BCOR-fusion, 2 years, n=15; BCOR-ITD, 1.8 years, n=55) and intermediate OS rates (BCOR-fusion, 6.8 years, n=18; BCOR-ITD 6.3 years, n=60). Further molecular and clinical characterization is ongoing potentially revealing first therapeutic leads for these highly aggressive CNS tumor types.
AB - Central nervous system (CNS) tumor with BCOR internal tandem duplication (BCOR-ITD) have recently been introduced in the 5th edition of the WHO classification of CNS tumors, however, their molecular makeup and clinical characteristics remain widely enigmatic. This is further complicated by the recent discovery of tumors characterized by gene fusions involving BCOR or its homologue BCORL1. We identified a cohort of 206 BCOR altered CNS tumors via DNA methylation profiling and conducted in-depth molecular and clinical characterization in an international effort. By performing t-SNE clustering analysis we found that BCOR-fusion tumors form a distinct cluster (n=61), adjacent to BCOR-ITD cases (n=145). The identified fusion partners of BCOR(L1) included EP300 (n=20), CREBBP (n=5), and NUTM2HP (n=1). Notably, three cases within the BCOR-ITD cluster harbored a c-terminal intragenic deletion within BCOR. With respect to clinical characteristics gender ratio was balanced in BCOR-fusion cases (m/f, 1.1), whereas predominance of male patients was observed in the BCOR-ITD group (m/f, 1.5). Moreover, age at diagnosis of BCOR-fusion patients was higher as compared to BCOR-ITD cases (15 vs 4.5 years). Interestingly, BCOR-fusion tumors were exclusively found in the supratentorial region being originally diagnosed as ependymomas or gliomas whereas BCOR-ITD emerged across the entire CNS with diverse original diagnoses. 8% of BCOR-ITD and none of BCOR-fusion cases were disseminated at diagnosis. In line with this observation, 40% of first relapses within the BCOR-ITD group were metastatic which was less frequent in BCOR-fusion tumors. Survival estimates demonstrated no differences, generally showing short median PFS (BCOR-fusion, 2 years, n=15; BCOR-ITD, 1.8 years, n=55) and intermediate OS rates (BCOR-fusion, 6.8 years, n=18; BCOR-ITD 6.3 years, n=60). Further molecular and clinical characterization is ongoing potentially revealing first therapeutic leads for these highly aggressive CNS tumor types.
UR - https://www.mendeley.com/catalogue/24a71f82-9358-36fe-9942-c68fbdd301bd/
U2 - 10.1093/neuonc/noac079.184
DO - 10.1093/neuonc/noac079.184
M3 - Article
SN - 1522-8517
VL - 24
SP - i50-i50
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - Supplement_1
ER -