Clinical and molecular characterization of HER2 amplified-pancreatic cancer

Angela Chou, Nicola Waddell, Mark J. Cowley, Anthony J. Gill, David K. Chang, Ann Marie Patch, Katia Nones, Jianmin Wu, Mark Pinese, Amber L. Johns, David K. Miller, Karin S. Kassahn, Adnan M. Nagrial, Harpreet Wasan, David Goldstein, Christopher W. Toon, Venessa Chin, Lorraine Chantrill, Jeremy Humphris, R. Scott Mead & 8 others Ilse Rooman, Jaswinder S. Samra, Marina Pajic, Elizabeth A. Musgrove, John V. Pearson, Adrienne L. Morey*, Sean M. Grimmond, Andrew V. Biankin

*Corresponding author for this work

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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.

Original languageEnglish
Article number78
Pages (from-to)1-11
Number of pages11
JournalGenome Medicine
Volume5
DOIs
Publication statusPublished - 31 Aug 2013
Externally publishedYes

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Copyright the Author(s) 2013. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Chou, A., Waddell, N., Cowley, M. J., Gill, A. J., Chang, D. K., Patch, A. M., ... Biankin, A. V. (2013). Clinical and molecular characterization of HER2 amplified-pancreatic cancer. Genome Medicine, 5, 1-11. [78]. https://doi.org/10.1186/gm482