title: Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines.
abstract: Breast cancer has for long been recognized as a highly diverse tumor group, but the underlying genetic basis has been elusive. Here, we report an extensive molecular characterization of a collection of 41 human breast cancer cell lines. Protein and gene expression analyses indicated that the collection of breast cancer cell lines has retained most, if not all, molecular characteristics that are typical for clinical breast cancers. Gene mutation analyses identified 146 oncogenic mutations among 27 well-known cancer genes, amounting to an average of 3.6 mutations per cell line. Mutations in genes from the p53, RB and PI3K tumor suppressor pathways were widespread among all breast cancer cell lines. Most important, we have identified two gene mutation profiles that are specifically associated with luminal-type and basal-type breast cancer cell lines. The luminal mutation profile involved E-cadherin and MAP2K4 gene mutations and amplifications of Cyclin D1, ERBB2 and HDM2, whereas the basal mutation profile involved BRCA1, RB1, RAS and BRAF gene mutations and deletions of p16 and p14ARF. These subtype-specific gene mutation profiles constitute a genetic basis for the heterogeneity observed among human breast cancers, providing clues for their underlying biology and providing guidance for targeted pharmacogenetic intervention in breast cancer patients.
authors: Department of Medical Oncology, Josephine Nefkens Institute, Erasmus, The Netherlands. a.hollestelle@erasmusmc.nl
authors: Antoinette
authors: A
authors: Hollestelle
authors: Jord H A
authors: JH
authors: Nagel
authors: Marcel
authors: M
authors: Smid
authors: Suzanne
authors: S
authors: Lam
authors: Fons
authors: F
authors: Elstrodt
authors: Marijke
authors: M
authors: Wasielewski
authors: Ser Sue
authors: SS
authors: Ng
authors: Pim J
authors: PJ
authors: French
authors: Justine K
authors: JK
authors: Peeters
authors: Marieke J
authors: MJ
authors: Rozendaal
authors: Muhammad
authors: M
authors: Riaz
authors: Daphne G
authors: DG
authors: Koopman
authors: Timo L M
authors: TL
authors: Ten Hagen
authors: Bertie H C G M
authors: BH
authors: de Leeuw
authors: Ellen C
authors: EC
authors: Zwarthoff
authors: Amina
authors: A
authors: Teunisse
authors: Peter J
authors: PJ
authors: van der Spek
authors: Jan G M
authors: JG
authors: Klijn
authors: Winand N M
authors: WN
authors: Dinjens
authors: Stephen P
authors: SP
authors: Ethier
authors: Hans
authors: H
authors: Clevers
authors: Aart G
authors: AG
authors: Jochemsen
authors: Michael A
authors: MA
authors: den Bakker
authors: John A
authors: JA
authors: Foekens
authors: John W M
authors: JW
authors: Martens
authors: Mieke
authors: M
authors: Schutte
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D009154:Mutation
chemical_list: D014408:Biomarkers, Tumor