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KRAS and BRAF Mutational Status in Primary Colorectal Tumors and Related Metastatic Sites: Biological and Clinical Implications
Ist Teil von
Annals of surgical oncology, 2010-05, Vol.17 (5), p.1429-1434
Ort / Verlag
New York: Springer-Verlag
Erscheinungsjahr
2010
Link zum Volltext
Quelle
SpringerLink (Online service)
Beschreibungen/Notizen
Background
KRAS
and
BRAF
mutations in primary colorectal tumors (PT) are predictive of nonresponse to anti–epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (mCRC). The question of primary resistance to anti-EGFR treatment as a result of the presence of
KRAS
or
BRAF
mutations only in metastases has been raised but not resolved.
Methods
We analyzed the mutational status of
KRAS
and
BRAF
in 64 new patients with mCRC and performed a systematic review of published data from 285 patients.
Results
A total of 285 and 95 matched PT/metastases were available for the analysis of the
KRAS
and the
BRAF
status, respectively. An identical mutational pattern of
KRAS
in PT and the matching metastases were reported in all the cases but 14 (5%). In six cases (2%),
KRAS
was mutated in the PT and wild type in the metastatic site, whereas in eight cases (3%),
KRAS
was wild type in the PT and mutated in the metastatic site. An identical mutational pattern of
BRAF
in PT and the matching metastases was reported in all but two cases (3%). In one case (1.5%),
BRAF
was mutated in the PT and wild type in the metastatic site, whereas in one case (1.5%),
BRAF
was wild type in the PT and mutated in the metastatic site.
Conclusions
The acquisition by metastases of a
KRAS
or a
BRAF
mutation that was not present in the PT is a rare event, occurring in 5% of cases of mCRC. This is not a frequent mechanism of primary resistance to anti-EGFR treatments in mCRC.