In summary then, this study has shown very discrete clustering of subsets of GIST based on miRNA profiles with evidence of some functional effects of these differentially expressed miRNAs, excellent clinico-pathological correlations and implications for post-transcriptional dysregulation in pediatric/WT GIST oncogenesis. selleckchem Supporting Information Table S1 Unpublished primers used in this study. Sequences of primers used for mutational analysis of KIT exon 17 and PDGFRA exons 12, 14, 18 indicating outer and semi-nested primers. (DOC) Click here for additional data file.(26K, doc) Acknowledgments Cases were received with gratitude from our fellow pathologists: Prof. Liliane Boccon-Gibod, Hopital d��Enfants Armand Trousseau, Paris, France; Dr. Abiel Orrego, Karolinska Institute, Sweden; Prof.

Neil Sebire, Great Ormond Street Children��s Hospital, London, UK; Dr. Meg Evans, Royal Infirmary of Edinburgh, Edinburgh, Scotland; Dr. Angeles Montero, Hospital Universitario Vall d��Hebron, Barcelona, Spain. We would like to thank especially John Darlow and Bronagh O hIci of the molecular genetics laboratory in the National Centre for Medical Genetics, who assisted with the HRM
The human KRAS oncogene is mutated in over 30% of CRC, and more than 3,000 point mutations have been reported to date [1]. The most frequent alterations are detected in codon 12 (~82% of all reported KRAS mutations) and in codon 13 (~17%), which are both in exon 2 of the KRAS gene [2] and appear to play a major role in the progression of CRC [3].

BRAF encodes a serine/thereonine kinase that activates the RAS-MAPK pathway, and its mutation have been found in 4�C15% of CRC. PIK3CA encodes the catalytic subunit p110 alpha of PI3K [4], and mutated PIK3CA stimulates the AKT pathway and promotes cell growth in various cancers, including CRC [5]. PIK3CA mutations have been described in 10%�C30% of CRC [6], and are associated with KRAS mutation. There has been a report that the presence of mutations in PIK3CA, KRAS, or BRAF in CRC showed worse patient outcome [7], and among patients who undergo a curative resection of CRC, PIK3CA mutation is associated with shorter cancer-specific survival [8]. However, the adverse effect of PIK3CA mutation may Entinostat be potentially limited to patients with KRAS wild-type tumors [8]. Cetuximab and panitumumab are effective epidermal growth factor receptor (EGFR) targeted agents for metastatic colorectal cancer (mCRC), but patients whose tumors have KRAS mutations except G13D [9] are generally believed to not benefit from these agents [10], [11]. Furthermore, mutations in BRAF and PIK3CA have also been reported to affect the efficacy of EGFR-targeted agents [12], [13].