Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumorReportar como inadecuado




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BMC Clinical Pathology

, 9:8

First Online: 15 October 2009Received: 15 June 2009Accepted: 15 October 2009

Abstract

BackgroundKRAS mutations represent key alterations in colorectal cancer development and lead to constitutive EGFR signaling. Since EGFR inhibition represents a therapeutic strategy in advanced colorectal cancer, KRAS mutation analysis has quickly been introduced as a treatment-predictive test.

MethodsWe used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 39% tumors.

ResultsKRAS mutations were significantly more often found in rectal cancer 21-38, 55% than in colon cancer 32-98, 33% P = 0.02. This finding was explained by marked differences mutation rates in female patients who showed mutations in 33% of the colon cancers and in 67% of the rectal cancers P = 0.01. Concurrent KRAS mutations were identified in three tumors; two colorectal cancers harbored Gly12Asp-Gly13Asp and Gly12Cys-Gly13Asp and a third tumor carried Gly12Cys-Gly12Asp in an adenomatous component and additionally acquired Gly12Val in the invasive component.

ConclusionThe demonstration of a particularly high KRAS mutation frequency among female rectal cancer patients suggests that this subset is the least likely to respond to anti-EGFR therapies, whereas the observation of concurrent KRAS mutations imply that repeated KRAS targeting may occur during tumor progression in a subset of colorectal cancers.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6890-9-8 contains supplementary material, which is available to authorized users.

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Autor: Mats Jönsson - Anna Ekstrand - Thomas Edekling - Jakob Eberhard - Dorthe Grabau - David Borg - Mef Nilbert

Fuente: https://link.springer.com/







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