title: Combined microRNA and ER expression: a new classifier for familial and sporadic breast cancer patients.
abstract: BACKGROUND
  The role of miRNAs in familial breast cancer (fBC) is poorly investigated as also in the BRCA-like tumors. To identify a specific miRNA expression pattern which could allow a better fBC classification not only based on clinico-pathological and immunophenotypical parameters we analyzed miRNA profile in familial and sporadic samples. Moreover since BRCA1 tumors and sporadic triple negative (TN) breast tumors share similarities regarding clinical outcomes and some histological characteristics, we focused on TN and not TN cases.
  
  
  METHODS
  The sample set included fresh frozen tissue samples, including 39 female fBCs (19 BRCA-related and 20 BRCAX) and 12 male fBC (BRCAX). Moreover, we considered TN and non TN (NTN), 21 BRCA-related and 27 sporadic BCs. MiRNA profiling was performed through GeneChip miRNA v.1.0 Array (Affymetrix). ANOVA, hierarchical and consensus clustering analyses allowed identification of pattern of expression of miRNAs and pathway enrichment analysis, considering validated target genes, was carried out to achieve a deeper biological understanding.
  
  
  RESULTS
  ANOVA test led to the identification of 53 deregulated miRNAs; hierarchical and consensus clustering of female fBCs (fFBCs) and male fBCs (fMBCs) highlighted the presence of 3 sample clusters named FBC1, FBC2 and FBC3. We found a correlation between ER-status and the three sample clusters. The three clusters are distinct by a different expression of two clusters of miRNAs (CLU1 and CLU2), which resulted to be different in targeted pathways. In particular, CLU1 targets cellular pathways and CLU2 is involved in epigenetic activities. Considering TN and NTN BRCA-related and sporadic tumors, a hierarchical clustering identified two clusters of miRNAs, which were not so different from CLU1 and CLU2, both in miRNA content and targeted pathways.
  
  
  CONCLUSIONS
  Our results highlighted the importance of miRNA regulation to better clarify similarities and differences between familial and sporadic BC groups.
authors.forename: Katia
authors.initials: K
authors.lastname: Danza
authors.forename: Simona
authors.initials: S
authors.lastname: De Summa
authors.forename: Brunella
authors.initials: B
authors.lastname: Pilato
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.forename: Ondina
authors.initials: O
authors.lastname: Popescu
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Pinto
authors.affiliation: Molecular Genetics Laboratory, IRCCS, Istituto Tumori "Giovanni Paolo II", v,le Orazio Flacco 65, Bari, 70124, Italy. s.tommasi@oncologico.bari.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018567:Breast Neoplasms, Male / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D011960:Receptors, Estrogen