Clonal relationships between lobular carcinoma in situ and other breast malignancies Journal Article


Authors: Begg, C. B.; Ostrovnaya, I.; Scarpa Carniello, J. V.; Sakr, R. A.; Giri, D.; Towers, R.; Schizas, M.; De Brot, M.; Andrade, V. P.; Mauguen, A.; Seshan, V. E.; King, T. A.
Article Title: Clonal relationships between lobular carcinoma in situ and other breast malignancies
Abstract: Background: 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. Methods: 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. Results: 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. Conclusions: 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. © 2016 The Author(s).
Keywords: breast cancer; lobular carcinoma in situ; whole-exome sequencing; clonal relatedness; copy number array; molecular pathology in clinical prevention; premalignant lesions
Journal Title: Breast Cancer Research
Volume: 18
Issue: 1
ISSN: 1465-5411
Publisher: Biomed Central Ltd  
Date Published: 2016-06-23
Start Page: 66
Language: English
DOI: 10.1186/s13058-016-0727-z
PROVIDER: scopus
PMCID: PMC4918003
PUBMED: 27334989
DOI/URL:
Notes: Article -- Export Date: 2 August 2016 -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    385 Seshan
  2. Colin B Begg
    306 Begg
  3. Dilip D Giri
    184 Giri
  4. Tari King
    186 King
  5. Rita Sakr
    61 Sakr
  6. Russell Towers
    13 Towers
  7. Michail Schizas
    27 Schizas
  8. Audrey   Mauguen
    157 Mauguen