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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 LU ; Isinger Ekstrand, Anna LU ; Edekling, Thomas; Eberhard, Jakob LU ; Grabau, Dorthe LU ; Borg, David LU and Nilbert, Mef LU (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
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Clinical Pathology
volume
9
issue
Oct 15
pages
8 - 8
publisher
BioMed Central
external identifiers
  • pmid:19832985
  • scopus:70449441671
ISSN
1472-6890
DOI
10.1186/1472-6890-9-8
language
English
LU publication?
yes
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
2009-11-03 13:29:11
date last changed
2017-06-18 04:41:45
@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>},
  articleno    = {8},
  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},
  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          = {http://dx.doi.org/10.1186/1472-6890-9-8},
  volume       = {9},
  year         = {2009},
}