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Genome Med. 2013 Aug 31;5(8):78. doi: 10.1186/gm482. eCollection 2013.

Clinical and molecular characterization of HER2 amplified-pancreatic cancer.

Author information

1
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.
2
Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
3
Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia ; St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
4
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.
5
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.
6
Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia.
7
Department of Cancer Medicine, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
8
Prince of Wales Clinical School, University of New South Wales and Prince of Wales Hospital, Sydney, Australia.
9
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.
10
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.
11
Upper Gastrointestinal Surgery Unit, Royal North Shore Hospital, Sydney, Australia.
12
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.
13
Anatomical Pathology, Sydpath, St Vincent's Hospital, Sydney, Australia.
14
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.

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.

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