Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis

Emilio Bria, Giampaolo Tortora, S. Pilotto, M. Simbolo, M. Fassan, G. De Manzoni, L. Carbognin, I. Sperduti, M. Brunelli, I. Cataldo, A. Tomezzoli, A. Mafficini, G. Turri, N. Karachaliou, R. Rosell, A. Scarpa

Risultato della ricerca: Contributo in rivistaArticolo in rivista

11 Citazioni (Scopus)

Abstract

In this study, we evaluated whether the presence of genetic alterations detected by next generation sequencing may define outcome in a prognostically-selected and histology-restricted population of resected gastric cancer (RGC). Intestinal type RGC samples from 34 patients, including 21 best and 13 worst prognostic performers, were studied. Mutations in 50 cancer-associated genes were evaluated. A significant difference between good and poor prognosis was found according to clinico-pathologic factors. The most commonly mutated genes in the whole population were PIK3CA (29.4%), KRAS (26.5%), TP53 (26.5%) MET (8.8%), SMAD4 (8.8%) and STK11 (8.8%). Multiple gene mutations were found in 14/21 (67%) patients with good prognosis, and 3/13 (23%) in the poor prognosis group. A single gene alteration was found in 5/21 (24%) good and 6/13 (46%) poor prognosis patients. No mutation was found in 2/21 (9.5%) and 4/13 (31%) of these groups, respectively. In the overall series, ß-catenin expression was the highest (82.4%), followed by E-Cadherin (76.5%) and FHIT (52.9%). The good prognosis group was characterized by a high mutation rate and microsatellite instability. Our proof-of-principle study demonstrates the feasibility of a molecular profiling approach with the aim to identify potentially druggable pathways and drive the development of customized therapies for RGC.
Lingua originaleEnglish
pagine (da-a)22982-22982
Numero di pagine1
RivistaScientific Reports
Volume6
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Aged
  • Aged, 80 and over
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Multidisciplinary
  • Mutation
  • Pathology, Molecular
  • Phosphatidylinositol 3-Kinases
  • Prognosis
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins p21(ras)
  • Smad4 Protein
  • Stomach Neoplasms
  • Tumor Suppressor Protein p53

Fingerprint

Entra nei temi di ricerca di 'Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis'. Insieme formano una fingerprint unica.

Cita questo