Title: KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy
Authors: Valtorta, Emanuele ×
Misale, Sandra
Sartore-Bianchi, Andrea
Nagtegaal, Iris D
Paraf, François
Lauricella, Calogero
Dimartino, Valentina
Hobor, Sebastijan
Jacobs, Bart
Ercolani, Cristiana
Lamba, Simona
Scala, Elisa
Veronese, Silvio
Laurent-Puig, Pierre
Siena, Salvatore
Tejpar, Sabine
Mottolese, Marcella
Punt, Cornelis Ja
Gambacorta, Marcello
Bardelli, Alberto
Di Nicolantonio, Federica #
Issue Date: Sep-2013
Publisher: Wiley-Liss
Series Title: International journal of cancer. Journal international du cancer vol:133 issue:5 pages:1259-65
Article number: 10.1002/ijc.28106
Abstract: KRAS mutations are the most common oncogenic event in colorectal (CRC) cancer progression and their occurrence is associated with lack of response to anti EGFR targeted therapies. Using preclinical models and patients' samples we recently reported that the emergence of KRAS mutations but also KRAS amplification is associated with acquired resistance to the EGFR inhibitors cetuximab or panitumumab. We reasoned that KRAS amplification may also be responsible for primary resistance to these agents. Furthermore, while the prevalence of KRAS mutations has been well established in CRC, little is known about the frequency of KRAS amplification in large CRC series. We performed a screening of 1039 CRC samples to assess the prevalence of KRAS amplification in this tumour type and further evaluated the role of this genetic alteration on the sensitivity to anti EGFR therapies. We detected KRAS amplification in 7/1039 (0.67%) and 1/102 evaluable CRC specimens and cell lines, respectively. KRAS amplification was mutually exclusive with KRAS mutations. Tumours or cell lines harbouring this genetic lesion are not responsive to anti-EGFR inhibitors. Although KRAS amplification is an infrequent event in CRC, it might be responsible for precluding response to anti-EGFR treatment in a small proportion of patients. © 2013 Wiley Periodicals, Inc.
ISSN: 0020-7136
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Digestive Oncology (+)
× corresponding author
# (joint) last author

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