title: Full sequencing of TP53 identifies identical mutations within in situ and invasive components in breast cancer suggesting clonal evolution.
abstract: In breast cancer, previous studies have suggested that somatic TP53 mutations are likely to be an early event. However, there are controversies regarding the cellular origin and linear course of breast cancer. The purpose of this study was to investigate tumor evolution in breast cancer by analyzing TP53 mutation status in tumors from various stages of the disease. The entire coding sequence of TP53 was sequenced in a cohort of pure ductal carcinoma in situ (DCIS), pure invasive cancer (≤15mm) and mixed lesions (i.e. invasive cancer with an in situ component). Of 118 tumor samples, 19 were found to harbor a TP53 mutation; 5 (15.6%) of the pure DCIS, 4 (10.5%) of the pure invasive cancers and 10 (20.8%) of the mixed lesions. In the mixed lesions, both the invasive and the DCIS components showed the same mutation in all 5 cases where the two components were successfully microdissected. Presence of the same mutation in both DCIS and invasive components from the same tumor indicates same cellular origin. The role of mutant TP53 in the progression of breast cancer is less clear and may vary between subtypes.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala SE 75105, Sweden.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhou
authors.forename: Aslaug A
authors.initials: AA
authors.lastname: Muggerud
authors.forename: Phuong
authors.initials: P
authors.lastname: Vu
authors.forename: Eldri U
authors.initials: EU
authors.lastname: Due
authors.forename: Therese
authors.initials: T
authors.lastname: Sørlie
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wärnberg
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016366:Open Reading Frames / Q000235:genetics*; D017354:Point Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53