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

Ilan Weinreb; Salvatore Piscuoglio; Luciano G Martelotto; Daryl Waggott; Charlotte K Y Ng; Bayardo Perez-Ordonez; Nicholas J Harding; Javier Alfaro; Kenneth C Chu; Agnes Viale; Nicola Fusco; Arnaud da Cruz Paula; Caterina Marchio; Rita A Sakr; Raymond Lim; Lester D R Thompson; Simion I Chiosea; Raja R Seethala; Alena Skalova; Edward B Stelow; Isabel Fonseca; Adel Assaad; Christine How; Jianxin Wang; Richard de Borja; Michelle Chan-Seng-Yue; Christopher J Howlett; Anthony C Nichols; Y Hannah Wen; Nora Katabi; Nicholas Buchner; Laura Mullen; Thomas Kislinger; Bradly G Wouters; Fei-Fei Liu; Larry Norton; John D McPherson; Brian P Rubin; Blaise A Clarke; Britta Weigelt; Paul C Boutros; Jorge S Reis-Filho

doi:10.1038/ng.3096

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

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

Authors

Ilan Weinreb¹, Salvatore Piscuoglio², Luciano G Martelotto², Daryl Waggott³, Charlotte K Y Ng², Bayardo Perez-Ordonez¹, Nicholas J Harding⁴, Javier Alfaro⁵, Kenneth C Chu⁴, Agnes Viale⁶, Nicola Fusco⁷, Arnaud da Cruz Paula⁸, Caterina Marchio², Rita A Sakr⁹, Raymond Lim², Lester D R Thompson¹⁰, Simion I Chiosea¹¹, Raja R Seethala¹¹, Alena Skalova¹², Edward B Stelow¹³, Isabel Fonseca¹⁴, Adel Assaad¹⁵, Christine How¹⁶, Jianxin Wang⁴, Richard de Borja⁴, Michelle Chan-Seng-Yue⁴, Christopher J Howlett¹⁷, Anthony C Nichols¹⁷, Y Hannah Wen², Nora Katabi², Nicholas Buchner¹⁸, Laura Mullen¹⁸, Thomas Kislinger¹⁹, Bradly G Wouters¹⁹, Fei-Fei Liu²⁰, Larry Norton²¹, John D McPherson²², Brian P Rubin²³, Blaise A Clarke¹, Britta Weigelt², Paul C Boutros²⁴, Jorge S Reis-Filho²⁵

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Amino Acid Sequence
Animals
Humans
Immunohistochemistry
Immunoprecipitation
Mice
Microscopy, Confocal
Models, Molecular*
Molecular Sequence Data
Mutagenesis
Mutation, Missense / genetics
NIH 3T3 Cells
Protein Kinase C / chemistry
Protein Kinase C / genetics*
Salivary Gland Neoplasms / genetics*
Salivary Gland Neoplasms / pathology
Sequence Alignment
Sequence Analysis, DNA

Substances

protein kinase D
Protein Kinase C

Associated data

SRA/SRP045782
SRA/SRP045785

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States