Open Access Highly Accessed Research

Clinical and molecular characterization of HER2 amplified-pancreatic cancer

Angela Chou123, Nicola Waddell6, Mark J Cowley13, Anthony J Gill145, David K Chang11213, Ann-Marie Patch6, Katia Nones6, Jianmin Wu13, Mark Pinese13, Amber L Johns1, David K Miller6, Karin S Kassahn6, Adnan M Nagrial13, Harpreet Wasan7, David Goldstein8, Christopher W Toon459, Venessa Chin13, Lorraine Chantrill1103, Jeremy Humphris1, R Scott Mead123, Ilse Rooman13, Jaswinder S Samra11, Marina Pajic13, Elizabeth A Musgrove112, John V Pearson6, Adrienne L Morey2*, Sean M Grimmond126* and Andrew V Biankin11213*

Author Affiliations

1 Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia

2 Anatomical Pathology, Sydpath, St Vincent’s Hospital, Sydney, Australia

3 St Vincent’s Clinical School, University of New South Wales, Sydney, Australia

4 Department of Anatomical Pathology, Royal North Shore Hospital, St Lenoards, Sydney, Australia

5 Sydney Medical School, University of Sydney, Sydney, Australia

6 Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, 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 Histopath Pathology, 97 Waterloo Road, North Ryde, NSW 2113, Australia

10 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 Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK

13 West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK

For all author emails, please log on.

Genome Medicine 2013, 5:78  doi:10.1186/gm482

Published: 31 August 2013

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.