title: Oncogenic transformation induced by cell-free nucleic acids circulating in plasma (genometastasis) remains after the surgical resection of the primary tumor: a pilot study.
abstract: BACKGROUND
  The oncogenic transformation by cell-free nucleic acids circulating in plasma has been named as genometastasis. The feasibility of this phenomenon has been demonstrated and now it is necessary to value the impact of this phenomenon and to determine what conditions could promote or inhibit it. The goal of this study was to examine the transforming ability of plasma from colorectal cancer patients in a long-term follow-up after the surgical excision of the primary tumor, and to try correlate it with the clinical picture of patients.
  
  
  METHODS
  Blood samples were taken from eight patients with K-ras-mutated colorectal tumors, who were under surgical primary tumor resection at least 2 years before. Plasma was isolated by two centrifugations and added to cultures of NIH-3T3 cells and human adipose-derived stem cells (hASCs). In two cases, plasma was separated from cells by a membrane with 0.4-μm pores. The presence of mutated and non-mutated human K-ras sequences was tested by real-time PCR in cultured cells. After 30 days, cells were subcutaneously injected into athymic nude mice in order to test their ability to generate tumors.
  
  
  RESULTS
  In four of the eight patients analyzed after surgery, tumor DNA was detected in plasma. Plasmas from three of them were able to oncogenically transform NIH-3T3 cells in culture and, when those cells were injected in mice, carcinomas were generated. After a 2-year follow-up, metastases were found in two of the three patients whose plasmas were able to transform cells, and in two of the four in whom plasma tumor DNA was not detected. Thus, after a mean follow-up of 29.5 months, only four of 13 patients (30.8%) were alive and disease-free.
  
  
  CONCLUSIONS
  Primary tumor resection does not assure a complete clean of blood of circulating oncogenes, in spite of a disease-free clinical picture. Moreover, in some cases plasma kept their oncogenic capabilities. The value of these findings as prognosis factor remains unclear and needs further investigations.
authors.affiliation: Servicio de Cirugía General, Hospital Universitario La Paz, Paseo Castellana 261, 28046 - Madrid, Spain. damian.garcia@uam.es
authors.forename: Damián
authors.initials: D
authors.lastname: García-Olmo
authors.forename: Dolores C
authors.initials: DC
authors.lastname: García-Olmo
authors.forename: Carolina
authors.initials: C
authors.lastname: Domínguez-Berzosa
authors.forename: Hector
authors.initials: H
authors.lastname: Guadalajara
authors.forename: Luz
authors.initials: L
authors.lastname: Vega
authors.forename: Mariano
authors.initials: M
authors.lastname: García-Arranz
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002474:Cell-Free System; D011905:Genes, ras; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery; D009696:Nucleic Acids / Q000097:blood*; D010865:Pilot Projects; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D009696:Nucleic Acids