Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story

Colin Kenny; Sabrina Bausenwein; Antonio Lazaro; Rhoikos Furtwängler; Saskia L M Gooskens; Marry van den Heuvel Eibrink; Christian Vokuhl; Ivo Leuschner; Norbert Graf; Manfred Gessler; Maureen J O'Sullivan

doi:10.1002/path.4693

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Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story

Journal article

Peer reviewed

Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story

Colin Kenny, Sabrina Bausenwein, Antonio Lazaro, Rhoikos Furtwängler, Saskia L M Gooskens, Marry van den Heuvel Eibrink, Christian Vokuhl, Ivo Leuschner, Norbert Graf, Manfred Gessler, …

The Journal of pathology, Vol.238(5), pp.617-620

04/2016

DOI: 10.1002/path.4693

PMID: 27000436

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Abstract

Internal tandem duplication within the BCOR gene sequence that encodes the PUFD domain, important in the formation of the non-canonical or variant polycomb repressor complex 1 (v-PRC1), was very recently described in 100% of 20 clear cell sarcomas of kidney (CCSKs). None of those 20 cases bore the YWHAE-NUTM2 transcript, previously described by us in CCSK, and which constitutes the only other recurrent genetic aberration observed in CCSK, prompting consideration that these mutations might be mutually exclusive in CCSK. We analysed a cohort of 159 CCSKs and can now not only confirm that there is indeed mutual exclusivity of these BCOR and YWHAE mutations, but also show that a substantial proportion (in this series 11.8%) of CCSKs bear neither mutation when tested by these assays, raising the possibility of distinct aetiologies for subsets of CCSK. Clinical differences observed between the subsets support this notion. As CCSK may show poor chemo-responsiveness, and current treatment protocols mandate the use of doxorubicin with its associated side-effects, advances in understanding the disease biology with a view to more targeted and personalized treatment is a pressing need.

Adolescent

Amino Acid Sequence

Biomarkers, Tumor - genetics

Child

Child, Preschool

DNA Mutational Analysis

Female

Gene Duplication

Gene Fusion

Genetic Predisposition to Disease

Humans

Infant

Kidney Neoplasms - drug therapy

Kidney Neoplasms - genetics

Kidney Neoplasms - pathology

Male

Molecular Sequence Data

Mutation

Phenotype

Prognosis

Proto-Oncogene Proteins - genetics

Repressor Proteins - genetics

Sarcoma, Clear Cell - drug therapy

Sarcoma, Clear Cell - genetics

Sarcoma, Clear Cell - pathology

Tandem Repeat Sequences

Details

Title: Subtitle: Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story
Creators: Colin Kenny - National Children’s Research Centre
Sabrina Bausenwein - Comprehensive Cancer Center Mainfranken
Antonio Lazaro - National Children’s Research Centre
Rhoikos Furtwängler - Saarland University
Saskia L M Gooskens - Princess Máxima Center
Marry van den Heuvel Eibrink - Princess Máxima Center
Christian Vokuhl - Kiel Paediatric Cancer Registry, Christian Albrechts University, 24105, Kiel, Germany
Ivo Leuschner - Kiel University
Norbert Graf - Saarland University
Manfred Gessler - Comprehensive Cancer Center Mainfranken
Maureen J O'Sullivan - National Children’s Research Centre
Resource Type: Journal article
Publication Details: The Journal of pathology, Vol.238(5), pp.617-620
DOI: 10.1002/path.4693
PMID: 27000436
ISSN: 0022-3417
eISSN: 1096-9896
Grant note: DOI: 10.13039/501100001590, name: Health Research Board, award: HRB/CSA‐2012‐13; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft, award: GE539/13
Language: English
Date published: 04/2016
Academic Unit: Surgery
Record Identifier: 9984322824302771

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