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SIR, We appreciate the comment from Dr Vauthey and colleagues (Vauthey et al, 2012) on our recently published article by Kawamoto et al (2012) titled ‘KRAS mutations in primary tumours and

post-FOLFOX metastatic lesions in cases of colorectal cancer’. The _KRAS_ mutation has been regarded as one of the major ‘driver mutations’ of colorectal cancer, and its frequency is high

(approximately 40%) regardless of the Dukes stage (Andreyev et al, 1998). However, the prognostic and predictive usefulness of _KRAS_ mutations is still controversial (Karapetis et al, 2008;

Van Cutsem et al, 2009; Yoshino et al, 2012). Although the suggestion raised by Dr Vauthey that adjuvant FOLFOX may provide a selection pressure favouring a chemotherapy-resistant subset

enriched for _KRAS_ mutation is interesting, we should consider it carefully. We closely examined the seven cases of stage III colorectal cancer (metastases appeared ‘after’ FOLFOX therapy)

in our data set and found that only two cases (28.6%) harboured _KRAS_ mutations. Meanwhile, among the 14 cases of stage IV cancer (metastases appeared ‘before’ FOLFOX therapy), 10 cases

(71.4%) harboured _KRAS_ codon 12 mutations and 2 additional cases had _KRAS_ A146V or _NRAS_ Q61H mutations in both primary and metastatic lesions. Therefore, we could not conclude that

_KRAS_ mutations were enriched in the cases that relapsed ‘after’ adjuvant FOLFOX therapy in our data set. However, we would like to emphasise that the frequency of _KRAS_ mutations among

the cases with ‘resectable’ metastases after FOLFOX therapy reported in our article was quite high. As we reported previously, the _KRAS_ mutation frequency of oxaliplatin-refractory

‘unresectable’ metastatic colorectal cancer in our institute was 70 out of 159 (44.0%), which is equivalent to the rates described in the previous reports (Bando et al, 2011). We cannot deny

that the mutant KRAS affected the biological features of metastasised tumours, and we plan further investigations. CHANGE HISTORY * _ 24 JANUARY 2013 This paper was modified 12 months after

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_N Engl J Med_ 359: 1757–1765 Article  CAS  Google Scholar  * Kawamoto Y, Tsuchihara K, Yoshino T, Ogasawara N, Kojima M, Takahashi M, Ochiai A, Bando H, Fuse N, Tahara M, Doi T, Esumi H,

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Scholar  * Yoshino T, Mizunuma N, Yamazaski K, Nishina T, Komatsu Y, Baba H, Tsuji A, Yamaguchi K, Muro K, Sugimoto N, Tsuji Y, Moriwaki T, Esaki T, Hamada C, Tanase T, Ohtsu A (2012)

TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double blind, randomized, placebo-controlled phase II trial. _Lancet Oncol_ ; e-pub ahead of print 28 August 2012 Download

references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Translational Research, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, 277-8577,

Japan T Yoshino, Y Kawamoto, H Bando & K Tsuchihara * Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, 277-8577, Japan T

Yoshino, Y Kawamoto & H Bando * Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan Y Kawamoto Authors * T Yoshino View author

publications You can also search for this author inPubMed Google Scholar * Y Kawamoto View author publications You can also search for this author inPubMed Google Scholar * H Bando View

author publications You can also search for this author inPubMed Google Scholar * K Tsuchihara View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to K Tsuchihara. RIGHTS AND PERMISSIONS From twelve months after its original publication, this work is licensed under the Creative Commons

Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ Reprints and permissions ABOUT THIS

ARTICLE CITE THIS ARTICLE Yoshino, T., Kawamoto, Y., Bando, H. _et al._ Reply: KRAS mutation in colorectal cancer metastases after adjuvant folfox for the primary. _Br J Cancer_ 107, 1444

(2012). https://doi.org/10.1038/bjc.2012.420 Download citation * Published: 27 September 2012 * Issue Date: 09 October 2012 * DOI: https://doi.org/10.1038/bjc.2012.420 SHARE THIS ARTICLE

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