title: [Carcinogenic pathways and natural history of upper tract urothelial carcinomas: state-of-the-art review for the yearly scientific report of the French National Association of Urology].
abstract: OBJECTIVE
  To describe natural history and carcinogenesis of upper tract urothelial carcinoma (UTUC).
  
  
  METHODS
  A systematic review of the scientific literature was performed in the Medline database (Pubmed) using different associations of the following keywords: upper tract urothelial carcinoma; clonality; carcinogenesis; mutation; chromosomal instability; Lynch syndrome; genetic polymorphism.
  
  
  RESULTS
  Local development of UTUC is characterized by a highly prevalent multifocality that might be explained by the overlap of "field change" and "intraluminal seeding and implantation" theories. UTUC and bladder tumors share common carcinogenesis mechanisms such as mutations of FGFR3 and TP53 defining two distinct pathways of pathogenesis. Epigenetic alterations corresponding to the hypermethylation of different promoters regulating genes expression and chromosomal instability such as chromosome 9 deletions are also involved in UTUC carcinogenesis. Furthermore, specific genetic risk factors fro UTUC including Lynch syndrome and different polymorphisms might explain an individual susceptibility for developing these tumors.
  
  
  CONCLUSIONS
  Significant advances have been done in the field of basic research in UTUCs in recent years and have been of particular interest to provide better descriptions of their natural history. Despite these important findings however, some carcinogenic mechanisms remains not elucidated and unknown in the field of UTUC so far.
authors.affiliation: Service d'urologie de l'hôpital de la Pitié-Salpétrière, AP-HP, 83, boulevard de l'Hôpital, 75013 Paris, France; GRC5, ONCOTYPE-URO, institut universitaire de cancérologie, UPMC université Paris 06, 75005 Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Seisen
authors.affiliation: GRC5, ONCOTYPE-URO, institut universitaire de cancérologie, UPMC université Paris 06, 75005 Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Cancel-Tassin
authors.affiliation: Service d'urologie de l'hôpital privé de La Louvière, générale de santé, 59000 Lille, France; Service d'urologie de l'hôpital de Seclin, 59113 Seclin, France.
authors.forename: P
authors.initials: P
authors.lastname: Colin
authors.affiliation: Service d'urologie de l'hôpital de la Pitié-Salpétrière, AP-HP, 83, boulevard de l'Hôpital, 75013 Paris, France; GRC5, ONCOTYPE-URO, institut universitaire de cancérologie, UPMC université Paris 06, 75005 Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Cussenot
authors.affiliation: Service d'urologie de l'hôpital de la Pitié-Salpétrière, AP-HP, 83, boulevard de l'Hôpital, 75013 Paris, France; GRC5, ONCOTYPE-URO, institut universitaire de cancérologie, UPMC université Paris 06, 75005 Paris, France. Electronic address: morgan.roupret@psl.aphp.fr.
authors.forename: M
authors.initials: M
authors.lastname: Rouprêt
mesh_terms: D063646:Carcinogenesis; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D043171:Chromosomal Instability; D003663:Decision Trees; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D055847:Lynch Syndrome II / Q000235:genetics; D009362:Neoplasm Metastasis; D009366:Neoplasm Seeding; D009857:Oncogenes / Q000235:genetics; D011110:Polymorphism, Genetic; D014571:Urologic Neoplasms / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*
keywords: Carcinogenesis; Carcinogenèse; Carcinome urothélial; Chromosomal instability; Clonal evolution; Clonalité; Genetic polymorphism; Instabilité chromosomique; Mutation; Mutations; Polymorphisme génétique; Renal pelvis; Syndrome de Lynch; Ureter; Urothelial carcinoma