title: Multistep transformation in low-grade lymphoproliferative diseases.
abstract: BACKGROUND
  Carcinogenesis, the formation of solid tumors, is now widely accepted to represent a multistep process. Several genetic events, activation of proto-oncogenes and inactivation of tumor suppressor genes, are involved.
  
  
  METHODS
  Review of the literature for evidence that the concept of multistep transformation has relevance also for the formation of low-grade lymphoproliferative diseases.
  
  
  CONCLUSIONS
  The common translocations in low-grade lymphoid tumors are probably early events, predominantly involved in the activation of oncogenes, leading to growth stimulation or prolonged cell survival. As a result 'monoclonal lymphoproliferative disorders of undetermined significance (MLDUS)' occur, undetermined, because some translocations may not always led to tumor formation. For progression to full malignancy, additional genetic events are required besides sequential selection of variant subpopulations within the neoplastic clone. Recent data indicate that mutations and deletions of putative tumor suppressor genes, including the P53 and retinoblastoma genes, are also involved in the progression of lymphoproliferative disorders. A list of lymphoproliferative diseases stressing this concept of multistep transformation is presented in this article.
authors.affiliation: Department of Research, University Hospital, Basel, Switzerland.
authors.forename: C U
authors.initials: CU
authors.lastname: Ludwig
authors.forename: M
authors.initials: M
authors.lastname: Gencik
authors.forename: R
authors.initials: R
authors.lastname: Shipman
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D009857:Oncogenes / Q000502:physiology; D013489:Suppression, Genetic