title: Clinical and molecular characterization of HER2 amplified-pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing of therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements in outcome. Although HER2 amplification occurs in pancreatic cancer, it is inadequately characterized to exploit the potential of anti-HER2 therapies.
  
  
  METHODS
  HER2 amplification was detected and further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined HER2 amplification in a large cohort of patients (n = 469) with pancreatic ductal adenocarcinoma (PDAC).
  
  
  RESULTS
  An amplified inversion event (1 MB) was identified at the HER2 locus in a patient with PDAC. Using standardized laboratory assays, we established diagnostic criteria for HER2 amplification in PDAC, and observed a prevalence of 2%. Clinically, HER2- amplified PDAC was characterized by a lack of liver metastases, and a preponderance of lung and brain metastases. Excluding breast and gastric cancer, the incidence of HER2-amplified cancers in the USA is >22,000 per annum.
  
  
  CONCLUSIONS
  HER2 amplification occurs in 2% of PDAC, and has distinct features with implications for clinical practice. The molecular heterogeneity of PDAC implies that even an incidence of 2% represents an attractive target for anti-HER2 therapies, as options for PDAC are limited. Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types.
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; Anatomical Pathology, Sydpath, St Vincent's Hospital, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Chou
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Nicola
authors.initials: N
authors.lastname: Waddell
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cowley
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; Department of Anatomical Pathology, Royal North Shore Hospital, St Lenoards, Sydney, Australia ; Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK ; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Chang
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Patch
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Katia
authors.initials: K
authors.lastname: Nones
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Pinese
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Johns
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: David K
authors.initials: DK
authors.lastname: Miller
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: Karin S
authors.initials: KS
authors.lastname: Kassahn
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Adnan M
authors.initials: AM
authors.lastname: Nagrial
authors.affiliation: Department of Cancer Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Wasan
authors.affiliation: Prince of Wales Clinical School, University of New South Wales and Prince of Wales Hospital, Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Department of Anatomical Pathology, Royal North Shore Hospital, St Lenoards, Sydney, Australia ; Sydney Medical School, University of Sydney, Sydney, Australia ; Histopath Pathology, 97 Waterloo Road, North Ryde, NSW 2113, Australia.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Toon
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Venessa
authors.initials: V
authors.lastname: Chin
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia ; Macarthur Cancer Therapy Centre, Sydney South West District Health Service, Sydney, NSW, Australia.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Chantrill
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Humphris
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; Anatomical Pathology, Sydpath, St Vincent's Hospital, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Mead
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Ilse
authors.initials: I
authors.lastname: Rooman
authors.affiliation: Upper Gastrointestinal Surgery Unit, Royal North Shore Hospital, Sydney, Australia.
authors.forename: Jaswinder S
authors.initials: JS
authors.lastname: Samra
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Marina
authors.initials: M
authors.lastname: Pajic
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Musgrove
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
authors.forename: John V
authors.initials: JV
authors.lastname: Pearson
authors.affiliation: Anatomical Pathology, Sydpath, St Vincent's Hospital, Sydney, Australia.
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: Morey
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.affiliation: Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK ; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin