title: Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection.
abstract: A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment.
  
  
  
  We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, TP53 and FBXW7 genes by HRM and Sanger sequencing analysis.
  
  
  
  Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS, PIK3CA, FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences (P=0.0005). In patients treated with abdominoperineal resection (APR) after relapse (n=38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status (P=0.048), gender (P=0.045) and PIK3CA mutation (P=0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis (P=0.025).
  
  
  
  Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA-mutated patients.
authors.affiliation: Department of Medical Oncology, Institut Curie, René Huguenin Hospital, 35 rue Dailly, 92210 Saint-Cloud, France.|Pharmacogenomics Unit, Department of Genetics, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Wulfran
authors.initials: W
authors.lastname: Cacheux
authors.affiliation: Pharmacogenomics Unit, Department of Genetics, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.affiliation: Pharmacogenomics Unit, Department of Genetics, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Briaux
authors.affiliation: Center of Oncology, University Hospital of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
authors.forename: Petros
authors.initials: P
authors.lastname: Tsantoulis
authors.affiliation: Department of Surgical Oncology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Mariani
authors.affiliation: Department of Radiation Oncology, Institut Curie, Reneé Huguenin Hospital, 35 rue Dailly, 92210 Saint-Cloud, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Richard-Molard
authors.affiliation: Department of Medical Oncology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.affiliation: Translational Research, Research Center, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.|IFR71, Faculty of Biologic and Pharmacologic Sciences, University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Dangles-Marie
authors.affiliation: Translational Research, Research Center, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Richon
authors.affiliation: Pharmacogenomics Unit, Department of Genetics, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lazartigues
authors.affiliation: Department of Pathology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jeannot
authors.affiliation: Department of Pathology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Farkhondeh
authors.affiliation: Department of Pathology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.affiliation: Department of Radiation Oncology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: de La Rochefordière
authors.affiliation: Department of Surgical Oncology, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Labib
authors.affiliation: Department of Public Health, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Falcou
authors.affiliation: Department of Public Health, Institut Curie, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Stevens
authors.affiliation: Center of Oncology, University Hospital of Geneva, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Roth
authors.affiliation: Translational Research, Research Center, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Sergio
authors.initials: S
authors.lastname: Roman-Roman
authors.affiliation: Department of Medical Oncology, Institut Curie, René Huguenin Hospital, 35 rue Dailly, 92210 Saint-Cloud, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mitry
authors.affiliation: Pharmacogenomics Unit, Department of Genetics, Institut Curie Hospital, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.affiliation: Department of Medical Oncology, Institut Curie, René Huguenin Hospital, 35 rue Dailly, 92210 Saint-Cloud, France.|Department of Gastroenterology, University Hospital of Rennes, University of Rennes 1, Rennes, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Lièvre
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human