Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.

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...

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Autores principales:	Sophie Eisenreich, Khalil Abou-El-Ardat, Karol Szafranski, Jaime A Campos Valenzuela, Andreas Rump, Janice M Nigro, Rolf Bjerkvig, Eva-Maria Gerlach, Karl Hackmann, Evelin Schröck, Dietmar Krex, Lars Kaderali, Gabriele Schackert, Matthias Platzer, Barbara Klink
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/801c70ba21a348528b99e6c36c4f4533
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spelling	oai:doaj.org-article:801c70ba21a348528b99e6c36c4f45332021-11-18T08:53:33ZNovel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.1932-620310.1371/journal.pone.0076623https://doaj.org/article/801c70ba21a348528b99e6c36c4f45332013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086756/?tool=EBIhttps://doaj.org/toc/1932-6203Oligodendroglial 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.Sophie EisenreichKhalil Abou-El-ArdatKarol SzafranskiJaime A Campos ValenzuelaAndreas RumpJanice M NigroRolf BjerkvigEva-Maria GerlachKarl HackmannEvelin SchröckDietmar KrexLars KaderaliGabriele SchackertMatthias PlatzerBarbara KlinkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e76623 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sophie Eisenreich Khalil Abou-El-Ardat Karol Szafranski Jaime A Campos Valenzuela Andreas Rump Janice M Nigro Rolf Bjerkvig Eva-Maria Gerlach Karl Hackmann Evelin Schröck Dietmar Krex Lars Kaderali Gabriele Schackert Matthias Platzer Barbara Klink Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.
description	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.
format	article
author	Sophie Eisenreich Khalil Abou-El-Ardat Karol Szafranski Jaime A Campos Valenzuela Andreas Rump Janice M Nigro Rolf Bjerkvig Eva-Maria Gerlach Karl Hackmann Evelin Schröck Dietmar Krex Lars Kaderali Gabriele Schackert Matthias Platzer Barbara Klink
author_facet	Sophie Eisenreich Khalil Abou-El-Ardat Karol Szafranski Jaime A Campos Valenzuela Andreas Rump Janice M Nigro Rolf Bjerkvig Eva-Maria Gerlach Karl Hackmann Evelin Schröck Dietmar Krex Lars Kaderali Gabriele Schackert Matthias Platzer Barbara Klink
author_sort	Sophie Eisenreich
title	Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.
title_short	Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.
title_full	Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.
title_fullStr	Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.
title_full_unstemmed	Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.
title_sort	novel cic point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/801c70ba21a348528b99e6c36c4f4533
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Novel CIC point mutations and an exon-spanning, homozygous deletion identified in oligodendroglial tumors by a comprehensive genomic approach including transcriptome sequencing.

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