Novel CIC Point Mutations and an Exon-Spanning, Homozygous Deletion Identified in Oligodendroglial Tumors by a Comprehensive Genomic Approach Including Transcriptome Sequencing

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Sophie Eisenreich - , Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)
  • Khalil Abou-El-Ardat - , Institut für Klinische Genetik (Autor:in)
  • Karol Szafranski - , Leibniz-Institut für Alternsforschung – Fritz-Lipmann-Institut (Autor:in)
  • Jaime A. Campos Valenzuela - , Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)
  • Andreas Rump - , Institut für Klinische Genetik (Autor:in)
  • Janice M. Nigro - , University of Bergen (Autor:in)
  • Rolf Bjerkvig - , University of Bergen (Autor:in)
  • Eva Maria Gerlach - , Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)
  • Karl Hackmann - , Institut für Klinische Genetik (Autor:in)
  • Evelin Schröck - , Institut für Klinische Genetik (Autor:in)
  • Dietmar Krex - , Klinik und Poliklinik für Neurochirurgie (Autor:in)
  • Lars Kaderali - , Medizinische Fakultät Carl Gustav Carus Dresden (Autor:in)
  • Gabriele Schackert - , Technische Universität Dresden (Autor:in)
  • Matthias Platzer - , Leibniz-Institut für Alternsforschung – Fritz-Lipmann-Institut (Autor:in)
  • Barbara Klink - , Institut für Klinische Genetik (Autor:in)

Abstract

Oligodendroglial tumors form a distinct subgroup of gliomas, characterized by a better response to treatment and prolonged overall survival. Most oligodendrogliomas and also some oligoastrocytomas are characterized by a unique and typical unbalanced translocation, der(1,19), resulting in a 1p/19q co-deletion. Candidate tumor suppressor genes targeted by these losses, CIC on 19q13.2 and FUBP1 on 1p31.1, were only recently discovered. We analyzed 17 oligodendrogliomas and oligoastrocytomas by applying a comprehensive approach consisting of RNA expression analysis, DNA sequencing of CIC, FUBP1, IDH1/2, and array CGH. We confirmed three different genetic subtypes in our samples: i) the "oligodendroglial" subtype with 1p/19q co-deletion in twelve out of 17 tumors; ii) the "astrocytic" subtype in three tumors; iii) the "other" subtype in two tumors. All twelve tumors with the 1p/19q co-deletion carried the most common IDH1 R132H mutation. In seven of these tumors, we found protein-disrupting point mutations in the remaining allele of CIC, four of which are novel. One of these tumors also had a deleterious mutation in FUBP1. Only by integrating RNA expression and array CGH data, were we able to discover an exon-spanning homozygous microdeletion within the remaining allele of CIC in an additional tumor with 1p/19q co-deletion. Therefore we propose that the mutation rate might be underestimated when looking at sequence variants alone. In conclusion, the high frequency and the spectrum of CIC mutations in our 1p/19q-codeleted tumor cohort support the hypothesis that CIC acts as a tumor suppressor in these tumors, whereas FUBP1 might play only a minor role.

Details

OriginalspracheEnglisch
Aufsatznummere76623
FachzeitschriftPLoS ONE
Jahrgang8
Ausgabenummer9
PublikationsstatusVeröffentlicht - 27 Sept. 2013
Peer-Review-StatusJa

Externe IDs

Scopus 84884691994
researchoutputwizard legacy.publication#55237
researchoutputwizard legacy.publication#54482
PubMed 24086756