%0 Journal Article
%T The Presence of Mutations in the K-RAS Gene Does Not Affect Survival after Resection of Pulmonary Metastases from Colorectal Cancer
%A Jon Zabaleta
%A Borja Aguinagalde
%A Jos¨¦ M. Izquierdo
%A Nerea Bazterargui
%A Stephany M. Laguna
%A Maialen Martin-Arruti
%A Carmen Lobo
%A Jos¨¦ I. Emparanza
%J ISRN Surgery
%D 2014
%R 10.1155/2014/157586
%X Introduction. Our objective was to identify mutations in the K-RAS gene in cases of pulmonary metastases from colorectal cancer (CRC) and determine whether their presence was a prognostic factor for survival. Methods. We included all patients with pulmonary metastases from CRC operated on between 1998 and 2010. K-RAS mutations were investigated by direct sequencing of DNA. Differences in survival were explored with the Kaplan-Meier method log-rank tests and multivariate Cox regression analysis. Results. 110 surgical interventions were performed on 90 patients. Factors significantly associated with survival were disease-free interval , age , number of metastases , lymph node involvement , size of the metastases , and previous liver metastasis . Searching in 79 patients, K-RAS mutations were found in 30 cases. We did not find statistically significant differences in survival comparing native and mutated K-RAS. We found a higher rate of lung recurrence and shorter time to recurrence in patients with K-RAS mutations. Gly12Asp mutation was associated with higher recurrence and lower survival . Conclusions. The presence of K-RAS mutations in pulmonary metastases does not affect overall survival but is associated with higher rates of pulmonary recurrence. 1. Introduction In general, the development of cancer is the consequence of a gradual accumulation of genetic alterations. These cause a progressive transformation of normal human cells into malignant cells [1]. The RAS family of genes have the highest known rate of mutations in human cancer, and the aberrant activation of the RAS gene due to a mutation leads to an overexpression of Ras proteins, causing changes in the cells that lead to proliferation, invasion, and metastasis [2]. The conversion of Ras of a protooncogene to an oncogene generally occurs as a consequence of a single mutation in the gene. The mutations are found most often in codon 12 of the gene, followed by condon 13 [3]. In the normal human gene, codon 12 has the sequence CGT that codes for the amino acid glycine (Gly). Any change leading to a loss of the Gly residue at codon 12 may change a normal Ras gene into one that is potentially carcinogenic [3]. Similarly, changes in the Gly residue at codon 13 have the same effect [3]. In recent years, researchers have identified over 20 oncogenes, mutations of which contribute to the occurrence of solid tumours in humans [4]. In colorectal carcinoma, the most common mutations are located in the K-RAS, PIK3CA, BRAF, and N-RAS genes [4]. Recently, Tie reported, in the journal Clinical Cancer
%U http://www.hindawi.com/journals/isrn.surgery/2014/157586/