title: Genetic Investigation of Uterine Carcinosarcoma: Case Report and Cohort Analysis.
abstract: BACKGROUND
  Uterine carcinosarcoma, a rare gynecological malignancy, often presents at the advanced stage with a poor prognosis because current therapies have not improved rates of survival. Genetic characterization of this tumor may lead to novel, specifically targeted drug targets to provide better treatment options for patients with this malignancy.
  
  
  METHODS
  We present a case of a woman aged 61 years with uterine carcinosarcoma and retrospectively analyzed 100 study patients with uterine carcinosarcoma. From this group, 9 study patients underwent targeted sequencing of 1,321 genes.
  
  
  RESULTS
  All 9 study patients had at least 1 mutation in JAK2, KRAS, PIK3CA, CTNNB1, PTEN, FBXW7, TP53, and ERBB2; of these, TP53 was the most frequently mutated gene (6/9). In addition, ARID1A and KMT2C, which have been described and identified as part of a set of chromatin-remodeling genes, were also found in our analyses. From our 100-person cohort clinical analyses, study patients with stage 1 cancer had a median survival rate of 33 months (95% confidence interval, 19-109) compared with a median survival rate of 6 months (95% confidence interval, 3-12) in those with stage 4 disease.
  
  
  CONCLUSIONS
  Disease stage alone predicted the rate of clinical survival. Up to 50% in the study group were identified at having early stage disease (stage 1/2), indicating improved rates of overall detection compared with previously reported data. Our mutational analysis findings add to the number of tumors in which these mutations have been found and suggest that chromatin-remodeling dysregulation may play a role in the tumorigenesis of carcinosarcoma.
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Hembree
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Teer
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Hakam
authors.affiliation: Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. Alberto.Chiappori@Moffitt.org.
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Chiappori
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D002296:Carcinosarcoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D016019:Survival Analysis; D014594:Uterine Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology