Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor. / Jönsson, Mats; Ekstrand, Anna; Edekling, Thomas; Eberhard, Jakob; Grabau, Dorthe; Borg, David; Nilbert, Mef; Jönsson, Mats; Ekstrand, Anna; Edekling, Thomas; Eberhard, Jakob; Grabau, Dorthe; Borg, David; Nilbert, Mef.
I: BMC Clinical Pathology, Bind 9, 2009, s. 8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor
AU - Jönsson, Mats
AU - Ekstrand, Anna
AU - Edekling, Thomas
AU - Eberhard, Jakob
AU - Grabau, Dorthe
AU - Borg, David
AU - Nilbert, Mef
AU - Jönsson, Mats
AU - Ekstrand, Anna
AU - Edekling, Thomas
AU - Eberhard, Jakob
AU - Grabau, Dorthe
AU - Borg, David
AU - Nilbert, Mef
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1186/1472-6890-9-8
DO - 10.1186/1472-6890-9-8
M3 - Journal article
C2 - 19832985
VL - 9
SP - 8
JO - BMC Clinical Pathology
JF - BMC Clinical Pathology
SN - 1472-6890
ER -
ID: 21454905