title: Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers.
abstract: BACKGROUND
  Oncogene amplification and overexpression occur in tumor cells. Amplification status may provide diagnostic and prognostic information and may lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12 and 20q13 are recurrently amplified in breast cancers.
  
  
  METHODS
  To assess the frequencies and clinical impact of amplifications, we analyzed 547 invasive breast tumors organized in a tissue microarray (TMA) by fluorescence in situ hybridization (FISH) and calculated correlations with histoclinical features and prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1; (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with MYC and ERBB2 commercial probes, respectively.
  
  
  RESULTS
  We observed amplification of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in 19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13Z (amplified at ZNF217 only) in 9.9%, and 20q13Co (co-amplification of two or three 20q13 loci) in 8.5% of cases. The 8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%), 20q13Z and 20q13Co (1.6%) regions. The 17q12 and 11q13 regions were never found amplified alone. The most frequent co-amplification was 8p12/11q13. Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification of 12p13 was associated with basal molecular subtype.
  
  
  CONCLUSIONS
  Our results establish the frequencies, prognostic impacts and subtype associations of various amplifications and co-amplifications in breast cancers.
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Département d'Oncologie Moléculaire, UMR599 Inserm/Institut Paoli-Calmettes, Marseille, France. letessiera@marseille.fnclcc.fr <letessiera@marseille.fnclcc.fr>
authors.forename: Anne
authors.initials: A
authors.lastname: Letessier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Sircoulomb
authors.forename: Christophe
authors.initials: C
authors.lastname: Ginestier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cervera
authors.forename: Florence
authors.initials: F
authors.lastname: Monville
authors.forename: Véronique
authors.initials: V
authors.lastname: Gelsi-Boyer
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Jeannine
authors.initials: J
authors.lastname: Geneix
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Christophe
authors.initials: C
authors.lastname: Zemmour
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002886:Chromosomes, Human, Pair 17; D002890:Chromosomes, Human, Pair 20; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005784:Gene Amplification; D005787:Gene Frequency; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000175:diagnosis; D011379:Prognosis; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers