LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR)
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LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR). / Korshunov, Andrey; Ryzhova, Marina; Jones, David T W; Northcott, Paul A; van Sluis, Peter; Volckmann, Richard; Koster, Jan; Versteeg, Rogier; Cowdrey, Cynthia J; Perry, Arie; Picard, Daniel; Rosenblum, Marc; Giangaspero, Felice; Aronica, Eleonora; Schüller, Ulrich; Hasselblatt, Martin; Collins, V Peter; Deimling, Andreas; Lichter, Peter; Huang, Annie; Pfister, Stefan M; Kool, Marcel.
in: ACTA NEUROPATHOL, Jahrgang 124, Nr. 6, 12.2012, S. 875-81.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR)
AU - Korshunov, Andrey
AU - Ryzhova, Marina
AU - Jones, David T W
AU - Northcott, Paul A
AU - van Sluis, Peter
AU - Volckmann, Richard
AU - Koster, Jan
AU - Versteeg, Rogier
AU - Cowdrey, Cynthia J
AU - Perry, Arie
AU - Picard, Daniel
AU - Rosenblum, Marc
AU - Giangaspero, Felice
AU - Aronica, Eleonora
AU - Schüller, Ulrich
AU - Hasselblatt, Martin
AU - Collins, V Peter
AU - Deimling, Andreas
AU - Lichter, Peter
AU - Huang, Annie
AU - Pfister, Stefan M
AU - Kool, Marcel
PY - 2012/12
Y1 - 2012/12
N2 - Embryonal tumor with multilayered rosettes (ETMR, previously known as ETANTR) is a highly aggressive embryonal CNS tumor, which almost exclusively affects infants and is associated with a dismal prognosis. Accurate diagnosis is of critical clinical importance because of its poor response to current treatment protocols and its distinct biology. Amplification of the miRNA cluster at 19q13.42 has been identified previously as a genetic hallmark for ETMR, but an immunohistochemistry-based assay for clinical routine diagnostics [such as INI-1 for atypical teratoid rhabdoid tumor (AT/RT)] is still lacking. In this study, we screened for an ETMR-specific marker using a gene-expression profiling dataset of more than 1,400 brain tumors and identified LIN28A as a highly specific marker for ETMR. The encoded protein binds small RNA and has been implicated in stem cell pluripotency, metabolism and tumorigenesis. Using an LIN28A specific antibody, we carried out immunohistochemical analysis of LIN28A in more than 800 childhood brain-tumor samples and confirmed its high specificity for ETMR. Strong LIN28A immunoexpression was found in all 37 ETMR samples tested, whereas focal reactivity was only present in a small (6/50) proportion of AT/RT samples. All other pediatric brain tumors were completely LIN28A-negative. In summary, we established LIN28A immunohistochemistry as a highly sensitive and specific, rapid, inexpensive diagnostic tool for routine pathological verification of ETMR.
AB - Embryonal tumor with multilayered rosettes (ETMR, previously known as ETANTR) is a highly aggressive embryonal CNS tumor, which almost exclusively affects infants and is associated with a dismal prognosis. Accurate diagnosis is of critical clinical importance because of its poor response to current treatment protocols and its distinct biology. Amplification of the miRNA cluster at 19q13.42 has been identified previously as a genetic hallmark for ETMR, but an immunohistochemistry-based assay for clinical routine diagnostics [such as INI-1 for atypical teratoid rhabdoid tumor (AT/RT)] is still lacking. In this study, we screened for an ETMR-specific marker using a gene-expression profiling dataset of more than 1,400 brain tumors and identified LIN28A as a highly specific marker for ETMR. The encoded protein binds small RNA and has been implicated in stem cell pluripotency, metabolism and tumorigenesis. Using an LIN28A specific antibody, we carried out immunohistochemical analysis of LIN28A in more than 800 childhood brain-tumor samples and confirmed its high specificity for ETMR. Strong LIN28A immunoexpression was found in all 37 ETMR samples tested, whereas focal reactivity was only present in a small (6/50) proportion of AT/RT samples. All other pediatric brain tumors were completely LIN28A-negative. In summary, we established LIN28A immunohistochemistry as a highly sensitive and specific, rapid, inexpensive diagnostic tool for routine pathological verification of ETMR.
KW - Adolescent
KW - Biomarkers, Tumor
KW - Brain Neoplasms
KW - Child
KW - Child, Preschool
KW - DNA-Binding Proteins
KW - Diagnosis, Differential
KW - Gene Expression Profiling
KW - Humans
KW - MicroRNAs
KW - Neoplasms, Germ Cell and Embryonal
KW - Neuroectodermal Tumors, Primitive
KW - Neuropil
KW - RNA-Binding Proteins
KW - Rhabdoid Tumor
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1007/s00401-012-1068-3
DO - 10.1007/s00401-012-1068-3
M3 - SCORING: Journal article
C2 - 23161096
VL - 124
SP - 875
EP - 881
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 6
ER -