KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer.
KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer.
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DOI：
10.1038/bjc.2012.218
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发表时间：
2012-07-10
影响因子：
8.8
通讯作者：
Ohtsu, A.
中科院分区：
文献类型：
--
作者：
Kawamoto, Y.;Tsuchihara, K.;Yoshino, T.;Ogasawara, N.;Kojima, M.;Takahashi, M.;Ochiai, A.;Bando, H.;Fuse, N.;Tahara, M.;Doi, T.;Esumi, H.;Komatsu, Y.;Ohtsu, A.
KRAS 突变是抗 EGFR 抗体疗法对转移性结直肠癌患者疗效的预测标记。尽管据报道 KRAS 的突变状态在原发性病变和转移性病变之间高度一致，但尚不清楚基因毒性化疗是否可能诱导额外的突变。对 21 名接受 FOLFOX 作为 III/IV 期结直肠癌根治性切除后辅助治疗的患者的总共 63 个病灶（23 个基线原发灶、18 个转移灶和 24 个治疗后转移灶）进行了检查。 DNA样本取自福尔马林固定石蜡包埋标本，并评估KRAS、NRAS、BRAF和PIK3CA突变。野生型和突变型 KRAS 密码子 12 和 13 的原发病变数量分别为 8 个和 13 个。无论患者背景、治疗持续时间和无病生存期如何，原发肿瘤和 FOLFOX 后转移灶之间的 KRAS 突变状态保持一致。此外，评估的其他基因的突变状态在原发性病变和转移性病变之间也一致。由于 FOLFOX 治疗不会改变预测生物标志物基因的突变状态，因此来自原发性肿瘤和 FOLFOX 后肿瘤转移的标本可能作为已知基因组生物标志物测试的有效 DNA 来源。
KRAS mutations are predictive markers for the efficacy of anti-EGFR antibody therapies in patients with metastatic colorectal cancer. Although the mutational status of KRAS is reportedly highly concordant between primary and metastatic lesions, it is not yet clear whether genotoxic chemotherapies might induce additional mutations. A total of 63 lesions (23 baseline primary, 18 metastatic and 24 post-treatment metastatic) from 21 patients who were treated with FOLFOX as adjuvant therapy for stage III/IV colorectal cancer following curative resection were examined. The DNA samples were obtained from formalin-fixed paraffin-embedded specimens, and KRAS, NRAS, BRAF and PIK3CA mutations were evaluated. The numbers of primary lesions with wild-type and mutant KRAS codons 12 and 13 were 8 and 13, respectively. The mutational status of KRAS remained concordant between the primary tumours and the post-FOLFOX metastatic lesions, irrespective of patient background, treatment duration and disease-free survival. Furthermore, the mutational statuses of the other genes evaluated were also concordant between the primary and metastatic lesions. Because the mutational statuses of predictive biomarker genes were not altered by FOLFOX therapy, specimens from both primary tumours and post-FOLFOX tumour metastases might serve as valid sources of DNA for known genomic biomarker testing.
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影响因子：
11.5
作者：
Baldus, Stephan E.;Schaefer, Karl-L.;Gabbert, Helmut E.
通讯作者：
Gabbert, Helmut E.
影响因子：
50.5
作者：
Spindler, K. -L. Garm;Pallisgaard, N.;Jakobsen, A.
通讯作者：
Jakobsen, A.
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：
Khambata-Ford, Shirin;Garrett, Christopher R.;Mauro, David J.
通讯作者：
Mauro, David J.
影响因子：
8.8
作者：
Frattini, M;Saletti, P;Romagnani, E;Martin, V;Molinari, F;Ghisletta, M;Camponovo, A;Etienne, L L;Cavalli, F;Mazzucchelli, L
通讯作者：
Mazzucchelli, L