Clinical and molecular characterization of HER2 amplified-pancreatic cancer

Chou, Angela, Waddell, Nicola, Cowley, Mark J., Gill, Anthony J., Chang, David K., Patch, Ann-Marie, Nones, Katia, Wu, Jianmin, Pinese, Mark, Johns, Amber L., Miller, David K., Kassahn, Karin S., Nagrial, Adnan M., Wasan, Harpreet, Goldstein, David, Toon, Christopher W., Chin, Venessa, Chantrill, Lorraine, Humphris, Jeremy, Mead, R. Scott, Rooman, Ilse, Samra, Jaswinder S., Pajic, Marina, Musgrove, Elizabeth A., Pearson, John V., Morey, Adrienne L., Grimmond, Sean M. and Biankin, Andrew V. (2013) Clinical and molecular characterization of HER2 amplified-pancreatic cancer. Genome Medicine, 5 8: 78.1-78.10. doi:10.1186/gm482

Author Chou, Angela
Waddell, Nicola
Cowley, Mark J.
Gill, Anthony J.
Chang, David K.
Patch, Ann-Marie
Nones, Katia
Wu, Jianmin
Pinese, Mark
Johns, Amber L.
Miller, David K.
Kassahn, Karin S.
Nagrial, Adnan M.
Wasan, Harpreet
Goldstein, David
Toon, Christopher W.
Chin, Venessa
Chantrill, Lorraine
Humphris, Jeremy
Mead, R. Scott
Rooman, Ilse
Samra, Jaswinder S.
Pajic, Marina
Musgrove, Elizabeth A.
Pearson, John V.
Morey, Adrienne L.
Grimmond, Sean M.
Biankin, Andrew V.
Title Clinical and molecular characterization of HER2 amplified-pancreatic cancer
Journal name Genome Medicine   Check publisher's open access policy
ISSN 1756-994X
Publication date 2013-08
Year available 2013
Sub-type Article (original research)
DOI 10.1186/gm482
Open Access Status DOI
Volume 5
Issue 8
Start page 78.1
End page 78.10
Total pages 11
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2014
Language eng
Formatted 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.

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).

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.

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.
Keyword Lung cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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