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Effect of Subtype of K-Ras Mutation on Survival in Resected Pancreatic Adenocarcinoma

Objective The purpose is to determine if the different Kras mutations found in pancreatic ductal adenocarcinoma (PDA) confer different survivals after adjuvant gemcitabine, docetaxel and capecitabine (GTX) therapy, a regimen that affects Kras signaling. Methods We evaluated the survival with the type of Kras mutation in 53 patients who had resected PDA. All patients were treated either with neoadjuvant or adjuvant GTX therapy. The types and frequencies of Kras mutations in our PDA patients were compared to those in the literature for PDA, lung cancer and colon cancer. Results We found that 79% of our patients had a mutation in Kras at codon 12, with replacement of the glycine for either aspartic acid (47%), valine (19%), arginine (9%) or cysteine (4%). Serine and alanine substitutions and codon 13 mutations were not found. The frequency of Kras mutations detected in PDA differs markedly from those found in lung and colon cancer. Our PDA patients with aspartic acid or valine substitutions for glycine 12 had more relapses (p=0.026). Summary The types and frequencies of Kras mutations are different in PDA from those observed in lung cancer or colon cancer. PDA patients with aspartic acid and valine have a poor survival, but it is not clear if all Kras mutations are equally detrimental as other mutation had fewer relapses. Larger sample sizes are needed to know different amino acid substitutions in Kras result in different responses or survivals with GTX or other therapy.

Author(s): Kyung Chu, William Sherman

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