title: Clonal relationships between lobular carcinoma in situ and other breast malignancies.
abstract: Recent evidence suggests that lobular carcinoma in situ (LCIS) can be a clonal precursor of invasive breast cancers of both the ductal and lobular phenotypes. We sought to confirm these findings with an extensive study of fresh frozen breast specimens from women undergoing mastectomy.
  
  
  
  Patients with a history of LCIS presenting for therapeutic mastectomy were identified prospectively. Frozen tissue blocks were collected, screened for lesions of interest, and subjected to microdissection and DNA extraction. Copy number profiling, whole-exome sequencing, or both were performed. Clonal relatedness was assessed using specialized statistical techniques developed for this purpose.
  
  
  
  After exclusions for genotyping failure, a total of 84 lesions from 30 patients were evaluated successfully. Strong evidence of clonal relatedness was observed between an LCIS lesion and the invasive cancer for the preponderance of cases with lobular carcinoma. Anatomically distinct in situ lesions of both ductal and lobular histology were also shown to be frequently clonally related.
  
  
  
  These data derived from women with LCIS with or without invasive cancer confirm that LCIS is commonly the clonal precursor of invasive lobular carcinoma and that distinct foci of LCIS frequently share a clonal origin, as do foci of LCIS and ductal carcinoma in situ.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. beggc@mskcc.org.
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Ostrovnaya
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Jose V Scarpa
authors.initials: JV
authors.lastname: Carniello
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Sakr
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Dilip
authors.initials: D
authors.lastname: Giri
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Towers
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Michail
authors.initials: M
authors.lastname: Schizas
authors.affiliation: Department of Pathology, Federal University of Minas Gerais, Avenida Presidente Antônio Carlos, 6627 - Pampulha, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: De Brot
authors.affiliation: Department of Pathology, AC Camargo Cancer Center, Rua Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, CEP 01509 - 010, Sao Paulo, Brazil.
authors.forename: Victor P
authors.initials: VP
authors.lastname: Andrade
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Mauguen
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Venkatraman E
authors.initials: VE
authors.lastname: Seshan
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Tari A
authors.initials: TA
authors.lastname: King
mesh_terms: D000071960:Breast Carcinoma In Situ / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D060965:Clonal Evolution / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D059472:Exome; D005260:Female; D005787:Gene Frequency; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008408:Mastectomy; D009154:Mutation
keywords: Breast cancer; Clonal relatedness; Copy number array; Lobular carcinoma in situ; Molecular pathology in clinical prevention; Premalignant lesions; Whole-exome sequencing