title: Comprehensive molecular portrait using next generation sequencing of resected intestinal-type gastric cancer patients dichotomized according to prognosis.
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.
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bria
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Pilotto
authors.affiliation: ARC-NET Applied Research on Cancer Center, University of Verona, Verona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Simbolo
authors.affiliation: ARC-NET Applied Research on Cancer Center, University of Verona, Verona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fassan
authors.affiliation: 1st Division of General Surgery, University of Verona, Verona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: de Manzoni
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Carbognin
authors.affiliation: Biostatistics, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Cataldo
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tomezzoli
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mafficini
authors.affiliation: Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Turri
authors.affiliation: Pangaea Biotech, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Karachaliou
authors.affiliation: Pangaea Biotech, Barcelona, Spain.|Instituto Oncológico Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain.|Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.|Molecular Oncology Research (MORe) Foundation, Barcelona, Spain.|Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Rosell
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tortora
authors.affiliation: ARC-NET Applied Research on Cancer Center, University of Verona, Verona, Italy.|Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D057089:Pathology, Molecular; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D051901:Smad4 Protein / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D051901:Smad4 Protein; D016159:Tumor Suppressor Protein p53; C117307:KRAS protein, human; C497796:SMAD4 protein, human; C495901:TP53 protein, human; C484760:PIK3CA protein, human; C491743:MET protein, human; C109790:STK11 protein, human