title: Are ER+PR+ and ER+PR- breast tumors genetically different? A CGH array study.
abstract: The estrogen receptor (ER) is a well-known predictor of breast cancer response to endocrine therapy. ER+ progesterone receptor (PR)- breast tumors have a poorer response to endocrine therapy and a more aggressive phenotype than ER+PR+ tumors. A comparative genomic hybridization array technique was used to examine 25 ER+PR+ and 23 ER+PR- tumors. Tissue microarrays composed of 50 ER+PR+ and 50 ER+PR- tumors were developed to validate the comparative genomic hybridization array results. The genes of interest were analyzed by fluorescence in situ hybridization. The ER+PR- group had a slightly different genomic profile when compared with ER+PR+ tumors. Chromosomes 17 and 20 contained the most overlapping gains, and chromosomes 3, 8, 9, 14, 17, 21, and 22 contained the most overlapping losses when compared with the ER+PR+ group. The gained regions, 17q23.2-q23.3 and 20q13.12, and the lost regions, 3p21.32-p12.3, 9pter-p13.2, 17pter-p12, and 21pter-q21.1, occurred at different alteration frequencies and were statistically significant in the ER+PR- tumors compared with the ER+PR+ tumors. ER+PR- breast tumors have a different genomic profile compared with ER+PR+ tumors. Differentially lost regions in the ER+PR- group included genes with tumor suppressor functions and genes involved in apoptosis, mitosis, angiogenesis, and cell spreading. Differentially gained regions included genes such as MAP3K3, RPS6KB1, and ZNF217. Amplification of these genes could contribute to resistance to apoptosis, increased activation of the PI3K/Akt/mTOR pathway, and the loss of PR in at least some ER+PR- tumors.
authors.affiliation: Pathology Service, Molecular Cytogenetics Laboratory, Hospital del Mar, IMIM, Barcelona, Spain.
authors.forename: Alma
authors.initials: A
authors.lastname: Carracedo
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.forename: Josep M
authors.initials: JM
authors.lastname: Corominas
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.forename: Bibiana I
authors.initials: BI
authors.lastname: Ferreira
authors.forename: Javier
authors.initials: J
authors.lastname: Suela
authors.forename: Ignasi
authors.initials: I
authors.lastname: Tusquets
authors.forename: Cristina
authors.initials: C
authors.lastname: Corzo
authors.forename: Marcel
authors.initials: M
authors.lastname: Segura
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Montserrat
authors.initials: M
authors.lastname: Arumi
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone