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Ena-DATASET-MUG-26-02-2014-10:25:52:632-26 - samples

ABSTRACT: In this study we performed whole genome sequencing of plasma DNA (plasma-Seq) of 19 plasma-DNA samples from a total of 10 patients treated with anti-EGFR therapy. We demonstrated that development of resistance to anti-EGFR therapies is frequently associated with focal amplifications of KRAS, MET, and ERBB2. We also showed that focal KRAS amplifications can be acquired in tumor genomes of patients under cytotoxic chemotherapy. Furthermore, we provide evidence that specific chromosomal polysomies, such as overrepresentations of 12p and 7p, harboring KRAS and EGFR, respectively, determine responsiveness to anti-EGFR therapy.

PROVIDER: EGAD00001000748 | EGA |

REPOSITORIES: EGA

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Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing.

Mohan Sumitra S Heitzer Ellen E Ulz Peter P Lafer Ingrid I Lax Sigurd S Auer Martina M Pichler Martin M Gerger Armin A Eisner Florian F Hoefler Gerald G Bauernhofer Thomas T Geigl Jochen B JB Speicher Michael R MR

PLoS genetics 20140327 3

Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such as cetuximab and panitumumab, have evolved to important therapeutic options in metastatic colorectal cancer (CRC). However, almost all patients with clinical response to anti-EGFR therapies show disease progression within a few months and little is known about mechanism and timing of resistance evolution. Here we analyzed plasma DNA from ten patients treated with anti-EGFR therapy by whole genome sequencing (plasma ...[more]

PMID: 24676216

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