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Mutation profiling of adenoid cystic carcinomas from multiple anatomical sites identifies mutations in the RAS pathway, but no KIT mutations

Artikel i vetenskaplig tidskrift
Författare Daniel Wetterskog
P. M. Wilkerson
D. N. Rodrigues
M. B. Lambros
K. Fritchie
Mattias K Andersson
R. Natrajan
A. Gauthier
S. Di Palma
S. Shousha
Z. Gatalica
C. Topfer
V. Vukovic
R. A'Hern
B. Weigelt
A. Vincent-Salomon
Göran Stenman
B. P. Rubin
J. S. Reis
Publicerad i Histopathology
Volym 62
Nummer/häfte 4
Sidor 543-550
ISSN 0309-0167
Publiceringsår 2013
Publicerad vid Institutionen för biomedicin, avdelningen för patologi
Sahlgrenska Cancer Center
Sidor 543-550
Språk en
Länkar dx.doi.org/10.1111/his.12050
Ämnesord adenoid cystic carcinoma; BRAF ; HRAS ; KIT ; sequencing
Ämneskategorier Patologi

Sammanfattning

Aims The majority of adenoid cystic carcinomas (AdCCs), regardless of anatomical site, harbour the MYB–NFIB fusion gene. The aim of this study was to characterize the repertoire of somatic genetic events affecting known cancer genes in AdCCs. Methods and results DNA was extracted from 13 microdissected breast AdCCs, and subjected to a mutation survey using the Sequenom OncoCarta Panel v1.0. Genes found to be mutated in any of the breast AdCCs and genes related to the same canonical molecular pathways, as well as KIT, a proto-oncogene whose protein product is expressed in AdCCs, were sequenced in an additional 68 AdCCs from various anatomical sites by Sanger sequencing. Using the Sequenom MassARRAY platform and Sanger sequencing, mutations in BRAF and HRAS were identified in three and one cases, respectively (breast, and head and neck). KIT, which has previously been reported to be mutated in AdCCs, was also investigated, but no mutations were identified. Conclusions Our results demonstrate that mutations in genes pertaining to the canonical RAS pathway are found in a minority of AdCCs, and that activating KIT mutations are either absent or remarkably rare in these cancers, and unlikely to constitute a driver and therapeutic target for patients with AdCC.

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