Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy.
Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy.
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DOI：
10.1155/2009/831626
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发表时间：
2009
影响因子：
--
通讯作者：
Müller-Hermelink HK
中科院分区：
文献类型：
--
作者：
Gattenlöhner S;Etschmann B;Kunzmann V;Thalheimer A;Hack M;Kleber G;Einsele H;Germer C;Müller-Hermelink HK
抗EGFR靶向治疗是治疗转移性结直肠癌（mCRC）的有效策略，但KRAS基因的激活突变与对该治疗的不良反应相关。因此，在选择EGFR靶向治疗的患者时采用KRAS突变分析，并且各种研究显示原发性CRC和相应转移灶的突变状态之间具有高度一致性。然而，尽管在使用酪氨酸激酶抑制剂等新药的情况下也会发生治疗相关耐药，但尚未阐明抗EGFR治疗对复发性mCRC中KRAS/BRAF突变状态本身的影响。因此，我们分析了抗EGFR治疗前后的21例mCRC，发现21例病例中有20例的KRAS/BRAF突变状态在治疗前后一致。在1例不一致病例中，进一步分析显示存在肿瘤嵌合体或多个原发性肿瘤，表明抗EGFR治疗对mCRC中的KRAS/BRAF突变状态无影响。此外，由于抗EGFR治疗的KRAS S wt基因型患者的预选已成为标准程序，因此我们的样本集可能是未来研究的基础，这些研究旨在确定除KRAS/BRAF突变外的潜在抗EGFR治疗诱导的遗传改变。
Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a K R A S wt genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations.
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影响因子：
6.4
作者：
OUDEJANS, JJ;SLEBOS, RJC;RODENHUIS, S
通讯作者：
RODENHUIS, S
影响因子：
45.3
作者：
Allegra, Carmen J.;Jessup, J. Milburn;Schilsky, Richard L.
通讯作者：
Schilsky, Richard L.
影响因子：
158.5
作者：
Cunningham, D;Humblet, Y;Van Cutsem, E
通讯作者：
Van Cutsem, E
影响因子：
45.3
作者：
Loupakis, Fotios;Pollina, Luca;Falcone, Alfredo
通讯作者：
Falcone, Alfredo
影响因子：
11.5
作者：
Reynolds, NA;Wagstaff, AJ
通讯作者：
Wagstaff, AJ