title: PTEN and other tumor suppressor gene mutations as secondary genetic alterations in synovial sarcoma.
abstract: Synovial sarcomas (SS) consistently show a characteristic chromosomal translocation, t(X;18)(p11;q11), which usually leads to the formation of 2 chimeric fusion transcripts, SYT-SSX1 and -SSX2. A recent multi-institutional retrospective study revealed that the SYT-SSX fusion type emerged as the only independent significant factor for overall survival in cases of SS. The aims of this study were; i). to investigate the frequency of PTEN gene alteration, ii). to evaluate whether the mutation status in various tumor suppressor genes (TSG) is responsible for the clinical and histologic heterogeneity in SS. Forty-nine cases of SS were examined for the presence of PTEN gene mutation by polymerase chain reaction - single-strand conformation polymorphism followed by DNA direct sequencing. The obtained data was combined with those of previously reported TSG mutations such as p53, adenomatous polyposis coli, and E-cadherin genes. Follow-up was available for 44 patients, and survival analysis was performed according to the mutation status of these TSG. PTEN mutations were detected in 7 cases (14.3%), and all of these were monophasic tumors. More than half of the mutations detected were located in exon 9, which has been shown to play a less important role in PTEN functioning, and the PTEN mutation was not associated with patients' prognosis. Mutations in these TSG other than silent mutations were detected in 20 out of 49 cases (40.8%), although the mutation status in TSG was not associated with overall survival rate in patients with SS. Secondary genetic alterations in these TSG seem to have a less important prognostic impact on patients with SS.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: Tomonari
authors.initials: T
authors.lastname: Takahira
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Matsuda
authors.forename: Akio
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D013584:Sarcoma, Synovial / Q000175:diagnosis / Q000235:genetics*; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human