Next Article in Journal
Rapid, Sensitive Detection of Bartonella quintana by Loop-Mediated Isothermal Amplification of the groEL Gene
Next Article in Special Issue
MicroRNAs, DNA Damage Response, and Cancer Treatment
Previous Article in Journal
Preparation of a Bis-GMA-Free Dental Resin System with Synthesized Fluorinated Dimethacrylate Monomers
Previous Article in Special Issue
Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt Signaling Pathway
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(12), 2015; doi:10.3390/ijms17122015

High Intra- and Inter-Tumoral Heterogeneity of RAS Mutations in Colorectal Cancer

1
Faculté de Médecine Pharmacie, Université de Poitiers, 86021 Poitiers, France
2
Département de Cancérologie Biologique, Centre Hospitalo-Universitaire de Poitiers, 86021 Poitiers, France
3
Département d’anatomopathologie, Centre Hospitalo-Universitaire de Poitiers, 86021 Poitiers, France
4
Département de Gastroentérologie, Centre Hospitalo-Universitaire de Poitiers, 86021 Poitiers, France
5
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, EA 4331, Université de Poitiers, 86021 Poitiers, France
6
INSERM1084, Laboratoire de Neurosciences Expérimentales et Cliniques, Université de Poitiers, 86021 Poitiers, France
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 5 September 2016 / Revised: 24 November 2016 / Accepted: 25 November 2016 / Published: 1 December 2016
(This article belongs to the Collection Advances in Molecular Oncology)
View Full-Text   |   Download PDF [1669 KB, uploaded 1 December 2016]   |  

Abstract

Approximately 30% of patients with wild type RAS metastatic colorectal cancer are non-responders to anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs), possibly due to undetected tumoral subclones harboring RAS mutations. The aim of this study was to analyze the distribution of RAS mutations in different areas of the primary tumor, metastatic lymph nodes and distant metastasis. A retrospective cohort of 18 patients with a colorectal cancer (CRC) was included in the study. Multiregion analysis was performed in 60 spatially separated tumor areas according to the pathological tumor node metastasis (pTNM) staging and KRAS, NRAS and BRAF mutations were tested using pyrosequencing. In primary tumors, intra-tumoral heterogeneity for RAS mutation was found in 33% of cases. Inter-tumoral heterogeneity for RAS mutation between primary tumors and metastatic lymph nodes or distant metastasis was found in 36% of cases. Moreover, 28% of tumors had multiple RAS mutated subclones in the same tumor. A high proportion of CRCs presented intra- and/or inter-tumoral heterogeneity, which has relevant clinical implications for anti-EGFR mAbs prescription. These results suggest the need for multiple RAS testing in different parts of the same tumor and/or more sensitive techniques. View Full-Text
Keywords: colorectal cancer; RAS mutation; intra-tumoral heterogeneity; inter-tumoral heterogeneity colorectal cancer; RAS mutation; intra-tumoral heterogeneity; inter-tumoral heterogeneity
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Jeantet, M.; Tougeron, D.; Tachon, G.; Cortes, U.; Archambaut, C.; Fromont, G.; Karayan-Tapon, L. High Intra- and Inter-Tumoral Heterogeneity of RAS Mutations in Colorectal Cancer. Int. J. Mol. Sci. 2016, 17, 2015.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top