title: Colorectal carcinomas and PTEN/MMAC1 gene mutations.
abstract: OBJECTIVE
  PTEN/MMAC1/TEP1 is a tumor suppressor gene encoding a dual-specificity protein phosphatase with homology to the cytoskeleton proteins, chicken tensin and bovine auxilin. PTEN mutations have been described in several types of human cancer. Recently, mutations at an (A)(6) repeat of PTEN exons 7 and 8 in colorectal cancer (CRC) patients with microsatellite instability have been detected. Moreover, an involvement of the transforming growth factor (TGF)-beta pathway in hereditary colorectal syndromes has been proposed.
  
  
  METHODS
  In this study, we analyzed the frequency of PTEN gene mutations in 36 CRC patients and 5 colon cancer cell lines. Furthermore, in 16 of 36 patients, microsatellite instability and TGF-beta receptor II analysis was possible. The study was performed by PCR and automated sequencing of the entire coding region of the PTEN gene.
  
  
  RESULTS
  About 17% of colon cancer patients and one of five (HSR 320) colon cancer cell lines had mutations. Mutations were detected only among patients with locally advanced or metastatic CRC. PTEN mutations were detected in three of five (60%) patients showing both microsatellite instability and TGF-beta receptor II mutations. These patients presented with advanced or metastatic CRC CONCLUSIONS: Overall, these results show that PTEN alteration together with TGF-beta pathway inactivation could contribute to tumorigenesis and metastatic spread of sporadic and microsatellite unstable CRC.
authors.affiliation: Medicine Laboratory, Campus Biomedico University, Via E. Longoni, 83-00155 Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Dicuonzo
authors.forename: S
authors.initials: S
authors.lastname: Angeletti
authors.forename: J
authors.initials: J
authors.lastname: Garcia-Foncillas
authors.forename: A
authors.initials: A
authors.lastname: Brugarolas
authors.forename: Y
authors.initials: Y
authors.lastname: Okrouzhnov
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.forename: G
authors.initials: G
authors.lastname: Tonini
authors.forename: G
authors.initials: G
authors.lastname: Lorino
authors.forename: M
authors.initials: M
authors.lastname: De Cesaris
authors.forename: A
authors.initials: A
authors.lastname: Baldi
mesh_terms: D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human