@article{b6e8ae00aabc11df928f000ea68e967b,
title = "Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor",
abstract = "BACKGROUND: KRAS 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. METHODS: We used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 (39%) tumors. RESULTS: KRAS 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. CONCLUSION: The 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.",
author = "Mats J{\"o}nsson and Anna Ekstrand and Thomas Edekling and Jakob Eberhard and Dorthe Grabau and David Borg and Mef Nilbert and Mats J{\"o}nsson and Anna Ekstrand and Thomas Edekling and Jakob Eberhard and Dorthe Grabau and David Borg and Mef Nilbert",
year = "2009",
doi = "10.1186/1472-6890-9-8",
language = "English",
volume = "9",
pages = "8",
journal = "BMC Clinical Pathology",
issn = "1472-6890",
publisher = "BioMed Central Ltd.",
}
