In:
BMC Clinical Pathology, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2009-12)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1472-6890
DOI:
10.1186/1472-6890-9-8
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2009
detail.hit.zdb_id:
2059861-0
