title: Integrated genomic and transcriptomic analysis of ductal carcinoma in situ of the breast.
abstract: OBJECTIVE
  To gain insight into genomic and transcriptomic subtypes of ductal carcinomas in situ of the breast (DCIS).
  
  
  METHODS
  We did a combined phenotypic and genomic analysis of a series of 57 DCIS integrated with gene expression profile analysis for 26 of the 57 cases.
  
  
  RESULTS
  Thirty-two DCIS exhibited a luminal phenotype; 21 were ERBB2 positive, and 4 were ERBB2/estrogen receptor (ER) negative with 1 harboring a bona fide basal-like phenotype. Based on a CGH analysis, genomic types were identified in this series of DCIS with the 1q gain/16q loss combination observed in 3 luminal DCIS, the mixed amplifier pattern including all ERBB2, 12 luminal and 2 ERBB2(-)/ER(-) DCIS, and the complex copy number alteration profile encompassing 14 luminal and 1 ERBB2(-)/ER(-) DCIS. Eight cases (8 of 57; 14%) presented a TP53 mutation, all being amplifiers. Unsupervised analysis of gene expression profiles of 26 of the 57 DCIS showed that luminal and ERBB2-amplified, ER-negative cases clustered separately. We further investigated the effect of high and low copy number changes on gene expression. Strikingly, amplicons but also low copy number changes especially on 1q, 8q, and 16q in DCIS regulated the expression of a subset of genes in a very similar way to that recently described in invasive ductal carcinomas.
  
  
  CONCLUSIONS
  These combined approaches show that the molecular heterogeneity of breast ductal carcinomas exists already in in situ lesions and further indicate that DCIS and invasive ductal carcinomas share genomic alterations with a similar effect on gene expression profile.
authors.affiliation: Institut Curie, Department of Tumor Biology, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Carlo
authors.initials: C
authors.lastname: Lucchesi
authors.forename: Nadège
authors.initials: N
authors.lastname: Gruel
authors.forename: Virginie
authors.initials: V
authors.lastname: Raynal
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.forename: Rémi
authors.initials: R
authors.lastname: Goudefroye
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
authors.forename: Rémy
authors.initials: R
authors.lastname: Salmon
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Thiery
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype
chemical_list: D014408:Biomarkers, Tumor