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Nat Genet. 2014 Nov;46(11):1166-9. doi: 10.1038/ng.3096. Epub 2014 Sep 21.

Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands.

Author information

1
Department of Pathology, University Health Network, Toronto, Ontario, Canada.
2
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
3
1] Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. [2] Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Onatrio, Canada. [3] Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
4
Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
5
1] Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. [2] Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Onatrio, Canada. [3] Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [4] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
6
Integrated Genomics Operation, Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
7
1] Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] School of Pathology, University of Milan, Milan, Italy.
8
1] Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Instituto Português de Oncologia, Oporto, Portugal.
9
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
10
Department of Pathology, Kaiser Permanente, Woodland Hills Medical Center, Woodland Hills, California, USA.
11
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
12
Department of Pathology and Laboratory Medicine, Charles University in Prague, Plzen, Czech Republic.
13
Department of Pathology, University of Virginia Medical Center, Charlottesville, Virginia, USA.
14
1] Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal. [2] Faculdade de Medicina de Lisboa, Lisbon, Portugal.
15
Department of Pathology, Virginia Mason Hospital and Seattle Medical Center, Seattle, Washington, USA.
16
1] Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Onatrio, Canada. [2] Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
17
Western University, London, Ontario, Canada.
18
Cancer Genomics Platform, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
19
1] Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Onatrio, Canada. [2] Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
20
1] Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Onatrio, Canada. [2] Campbell Family Institute for Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [4] Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada.
21
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
22
1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [2] Department of Pathology, Virginia Mason Hospital and Seattle Medical Center, Seattle, Washington, USA.
23
1] Department of Molecular Genetics, Lerner Research Institute, Cleveland, Ohio, USA. [2] Robert J. Tomsich Pathology and Laboratory Medicine Institute, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio, USA.
24
1] Informatics and Bio-Computing Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [3] Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
25
1] Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2].

Abstract

Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.

PMID:
25240283
DOI:
10.1038/ng.3096
[Indexed for MEDLINE]
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