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Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.
Palomba, Grazia; Doneddu, Valentina; Cossu, Antonio; Paliogiannis, Panagiotis; Manca, Antonella; Casula, Milena; Colombino, Maria; Lanzillo, Annamaria; Defraia, Efisio; Pazzola, Antonio; Sanna, Giovanni; Putzu, Carlo; Ortu, Salvatore; Scartozzi, Mario; Ionta, Maria Teresa; Baldino, Giovanni; Sarobba, Giuseppina; Capelli, Francesca; Sedda, Tito; Virdis, Luciano; Barca, Michela; Gramignano, Giulia; Budroni, Mario; Tanda, Francesco; Palmieri, Giuseppe.
Affiliation
  • Palomba G; Institute of Biomolecular Chemistry, CNR, Sassari, Italy.
  • Doneddu V; Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Viale San Pietro 43, 07100, Sassari, PC, Italy.
  • Cossu A; Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Viale San Pietro 43, 07100, Sassari, PC, Italy.
  • Paliogiannis P; Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Viale San Pietro 43, 07100, Sassari, PC, Italy. panospaliogiannis@gmail.com.
  • Manca A; Institute of Biomolecular Chemistry, CNR, Sassari, Italy.
  • Casula M; Institute of Biomolecular Chemistry, CNR, Sassari, Italy.
  • Colombino M; Institute of Biomolecular Chemistry, CNR, Sassari, Italy.
  • Lanzillo A; Oncology Unit, Businco Hospital, Cagliari, Italy.
  • Defraia E; Oncology Unit, Businco Hospital, Cagliari, Italy.
  • Pazzola A; Medical Oncology Unit, University-Hospital of Sassari (AOU), Sassari, Italy.
  • Sanna G; Medical Oncology Unit, University-Hospital of Sassari (AOU), Sassari, Italy.
  • Putzu C; Medical Oncology Unit, University-Hospital of Sassari (AOU), Sassari, Italy.
  • Ortu S; Oncology Unit, Local Health Agency, Olbia, Italy.
  • Scartozzi M; Department of Medical Oncology, University of Cagliari, Cagliari, Italy.
  • Ionta MT; Department of Medical Oncology, University of Cagliari, Cagliari, Italy.
  • Baldino G; Oncology Unit, Civil Hospital, Alghero, Italy.
  • Sarobba G; Oncology Unit, Zonchello Hospital, Nuoro, Italy.
  • Capelli F; Oncology Unit, Zonchello Hospital, Nuoro, Italy.
  • Sedda T; Oncology Unit, Local Health Agency, Oristano, Italy.
  • Virdis L; Oncology Unit, Local Health Agency, Carbonia-Iglesias, Italy.
  • Barca M; Oncology Unit, Local Health Agency, Lanusei, Italy.
  • Gramignano G; Oncology Unit, Local Health Agency, Lanusei, Italy.
  • Budroni M; Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Viale San Pietro 43, 07100, Sassari, PC, Italy.
  • Tanda F; Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Viale San Pietro 43, 07100, Sassari, PC, Italy.
  • Palmieri G; Institute of Biomolecular Chemistry, CNR, Sassari, Italy.
J Transl Med ; 14(1): 292, 2016 10 13.
Article in En | MEDLINE | ID: mdl-27737711
BACKGROUND: Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population. METHODS: A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study. Genomic DNA was isolated from formalin-fixed, paraffin-embedded primary tumour tissue samples of CRC patients and screened for mutations in RAS and BRAF genes, using pyrosequencing assays, and in PIK3CA gene, using automated DNA sequencing assays. RESULTS: Overall, mutation rates were 35.6 % for KRAS, 4.1 % for NRAS, and 2.1 % for BRAF. Among available DNA samples, 114/796 (14.3 %) primary CRCs were found to carry a mutation in the PIK3CA gene. In this subset of patients analysed in all four genes, a pathogenetic mutation of at least one gene was discovered in about half (378/796; 47.5 %) of CRC cases. A mutated BRAF gene was found to steadily act as a negative prognostic factor for either time to progression as metastatic disease (from detection of primary CRC to diagnosis of first distant metastasis; p = 0.009) or partial survival (from diagnosis of advanced disease to the time of death or last control; p = 0.006) or overall survival (p < 0.001). No significant impact on prognosis was observed for mutated KRAS, NRAS, and PIK3CA genes or combined RAS mutations (all RAS). CONCLUSIONS: Our study defines both prevalence and prognostic role of main activated oncogenes in a population-based large collection of CRC patients.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Proto-Oncogene Proteins p21(ras) / Proto-Oncogene Proteins B-raf / Class I Phosphatidylinositol 3-Kinases / GTP Phosphohydrolases / Membrane Proteins / Mutation Type of study: Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: J Transl Med Year: 2016 Document type: Article Affiliation country: Italy Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Proto-Oncogene Proteins p21(ras) / Proto-Oncogene Proteins B-raf / Class I Phosphatidylinositol 3-Kinases / GTP Phosphohydrolases / Membrane Proteins / Mutation Type of study: Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: J Transl Med Year: 2016 Document type: Article Affiliation country: Italy Country of publication: United kingdom