Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor
(2009) In BMC Clinical Pathology 9(Oct 15). p.8-8- 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... (More)
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.
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- author
- Jönsson, Mats LU ; Isinger Ekstrand, Anna LU ; Edekling, Thomas ; Eberhard, Jakob LU ; Grabau, Dorthe LU ; Borg, David LU and Nilbert, Mef LU
- organization
- publishing date
- 2009-10-15
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Clinical Pathology
- volume
- 9
- issue
- Oct 15
- article number
- 8
- pages
- 8 - 8
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:19832985
- scopus:70449441671
- pmid:19832985
- ISSN
- 1472-6890
- DOI
- 10.1186/1472-6890-9-8
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Surgery (013242200), Oncology, MV (013035000), Pediatrics/Urology/Gynecology/Endocrinology (013240400), Division V (013230900), Department of Immunotechnology (011029300)
- id
- 9d02096f-9785-4aeb-aa0d-2b19058b70a7 (old id 1500312)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19832985?dopt=Abstract
- date added to LUP
- 2016-04-04 09:04:29
- date last changed
- 2022-01-29 08:06:40
@article{9d02096f-9785-4aeb-aa0d-2b19058b70a7, abstract = {{<p>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.</p><p>METHODS: We used a real-time PCR based method to determine KRAS mutations in 136 colorectal cancers with mutations identified in 53 (39%) tumors.</p><p>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.</p><p>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.</p>}}, author = {{Jönsson, Mats and Isinger Ekstrand, Anna and Edekling, Thomas and Eberhard, Jakob and Grabau, Dorthe and Borg, David and Nilbert, Mef}}, issn = {{1472-6890}}, language = {{eng}}, month = {{10}}, number = {{Oct 15}}, pages = {{8--8}}, publisher = {{BioMed Central (BMC)}}, series = {{BMC Clinical Pathology}}, title = {{Experiences from treatment-predictive KRAS testing; high mutation frequency in rectal cancers from females and concurrent mutations in the same tumor}}, url = {{https://lup.lub.lu.se/search/files/5224576/1502915.pdf}}, doi = {{10.1186/1472-6890-9-8}}, volume = {{9}}, year = {{2009}}, }