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KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer

BACKGROUND: 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 chemo...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394966/
https://www.ncbi.nlm.nih.gov/pubmed/22617127
http://dx.doi.org/10.1038/bjc.2012.218
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author 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
author_facet 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
author_sort Kawamoto, Y
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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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spelling pubmed-33949662012-07-12 KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer 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 Br J Cancer Molecular Diagnostics BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Nature Publishing Group 2012-07-10 2012-05-22 /pmc/articles/PMC3394966/ /pubmed/22617127 http://dx.doi.org/10.1038/bjc.2012.218 Text en Copyright © 2012 Cancer Research UK https://creativecommons.org/licenses/by-nc-sa/3.0/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/
spellingShingle Molecular Diagnostics
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 mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer
title KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer
title_full KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer
title_fullStr KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer
title_full_unstemmed KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer
title_short KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer
title_sort kras mutations in primary tumours and post-folfox metastatic lesions in cases of colorectal cancer
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394966/
https://www.ncbi.nlm.nih.gov/pubmed/22617127
http://dx.doi.org/10.1038/bjc.2012.218
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