title: Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions.
abstract: BACKGROUND
  Lobular carcinoma in situ (LCIS) has been accepted as a marker of risk for the development of invasive breast cancer, yet modern models of breast carcinogenesis include LCIS as a precursor of low-grade carcinomas. We provide evidence favoring a clonal origin for LCIS and synchronous estrogen receptor-positive malignant lesions of the ductal and lobular phenotype.
  
  
  METHODS
  Patients with prior LCIS undergoing mastectomy were identified preoperatively from 2003 to 2008. Specimens were widely sampled, and frozen blocks were screened for LCIS and co-existing malignant lesions, and were subject to microdissection. Samples from 65 patients were hybridized to the Affymetrix SNP 6.0 array platform. Cases with both an LCIS sample and an associated ductal carcinoma in situ (DCIS) or invasive tumor sample were evaluated for patterns of somatic copy number changes to assess evidence of clonal relatedness.
  
  
  RESULTS
  LCIS was identified in 44 of the cases, and among these a DCIS and/or invasive lesion was also identified in 21 cases. A total of 17 tumor pairs had adequate DNA/array data for analysis, including nine pairs of LCIS/invasive lobular cancer, four pairs of LCIS/DCIS, and four pairs of LCIS/invasive ductal cancer. Overall, seven pairs (41%) were judged to be clonally related; in five (29%) evidence suggested clonality but was equivocal, and five (29%) were considered independent. Clonal pairs were observed with all matched lesion types and low and high histological grades. We also show anecdotal evidence of clonality between a patient-matched triplet of LCIS, DCIS, and invasive ductal cancer.
  
  
  CONCLUSIONS
  Our results support the role of LCIS as a precursor in the development of both high-grade and low-grade ductal and lobular cancers.
authors: Victor P
authors: VP
authors: Andrade
authors: Irina
authors: I
authors: Ostrovnaya
authors: Venkatraman E
authors: VE
authors: Seshan
authors: Mary
authors: M
authors: Morrogh
authors: Dilip
authors: D
authors: Giri
authors: Narciso
authors: N
authors: Olvera
authors: Marina
authors: M
authors: De Brot
authors: Monica
authors: M
authors: Morrow
authors: Colin B
authors: CB
authors: Begg
authors: Tari A
authors: TA
authors: King
mesh_terms: D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002278:Carcinoma in Situ; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D060965:Clonal Evolution; D056915:DNA Copy Number Variations; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness
chemical_list: D014408:Biomarkers, Tumor