title: Whole-genome profiling helps to classify phyllodes tumours of the breast.
abstract: OBJECTIVE
  The aim of this study was to analyse a series of borderline and malignant phyllodes tumours (PTs) of the breast by whole-genome profiling to identify genomic markers that could help to recognise potentially malignant tumours within borderline tumours.
  
  
  METHODS
  We evaluated the genetic imbalances of a series of 53 PTs (30 borderline, 23 malignant) using the Human CNV370 BeadChip microarray (Illumina), containing 370 000 SNP markers and correlate this alterations with clinicopathological features.
  
  
  RESULTS
  Forty-five PTs (85%) showed chromosome copy number variations (CNVs). Twenty PTs (37%) showed five or more chromosomal imbalances (8/30 borderline (27%) and 12/23 malignant (52%)). The large-scale genetic changes associated with malignant were+7p (9/23), +1q (8/23), -10p (8/23), -13q14 (7/23), +8q (6/23) and +10q (6/23) and borderline were+1q (13/30), -13q14 (9/30), -6q (8/30) and -10p (8/30). Losses in 9p21.3, encompassing CDKN2A/B gene, were present in three tumours (malignant), whereas deletions of 13q, with a minimal region in 13q14.2 encompassing the RB1 gene, were found in 9/30 borderline and 7/28 malignant tumours. High-level amplifications were seen in eight tumours (seven malignant and one borderline): in 7p in three tumours (including EGFR in two), 7q31.2 (including TFEC and MET), 8q24.21 (including MYC) and 8q23.3 (including CSMD3) in one tumour each.
  
  
  CONCLUSIONS
  Whole-genome profiling by SNP arrays in PTs leads to identify a high number of CNV, gains of 7p and 8q, losses of 13q and 10, losses in 9p21.3 (CDKN2A/B) and the presence of amplifications, especially involving EGFR, as markers of potentially malignant tumours.
authors.affiliation: Service de Pathologie, Institut Curie, PSL Research University, Paris, France.
authors.forename: Marick
authors.initials: M
authors.lastname: Laé
authors.affiliation: Institut Curie, Paris, France.|PSL Research University, Paris, France.|Inserm, U900, Paris, France.|Mines Paris Tech, Fontainebleau, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: La Rosa
authors.affiliation: Institut Curie, Paris, France.|PSL Research University, Paris, France.|Inserm, U900, Paris, France.|Mines Paris Tech, Fontainebleau, France.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mandel
authors.affiliation: Service de chirurgie et SIRIC, Institut Curie, PSL Research University, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.affiliation: Institut Curie, Paris, France.|PSL Research University, Paris, France.|Inserm, U900, Paris, France.|Mines Paris Tech, Fontainebleau, France.|CNRS, UMR 144, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hupé
authors.affiliation: Service de Pathologie, Institut Gustave Roussy, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.affiliation: Service de Génétique, Institut Curie, PSL Research University, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Couturier
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics*; D002869:Chromosome Aberrations; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D003557:Phyllodes Tumor / Q000145:classification / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D014408:Biomarkers, Tumor; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: BREAST PATHOLOGY; CYTOGENETICS; MOLECULAR PATHOLOGY