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. 2016 Jun 23;18(1):66.
doi: 10.1186/s13058-016-0727-z.

Clonal relationships between lobular carcinoma in situ and other breast malignancies

Colin B Begg  1 , Irina Ostrovnaya  2 , Jose V Scarpa Carniello  3 , Rita A Sakr  3 , Dilip Giri  4 , Russell Towers  3 , Michail Schizas  3 , Marina De Brot  5 , Victor P Andrade  6 , Audrey Mauguen  2 , Venkatraman E Seshan  2 , Tari A King  3
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Clonal relationships between lobular carcinoma in situ and other breast malignancies

Colin B Begg et al. Breast Cancer Res. .

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.

Keywords: Breast cancer; Clonal relatedness; Copy number array; Lobular carcinoma in situ; Molecular pathology in clinical prevention; Premalignant lesions; Whole-exome sequencing.

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Figures

Fig. 1
Fig. 1
Copy number comparisons for case 33. Plots show similar copy number aberrations in both invasive lobular carcinoma (ILC) and lobular carcinoma in situ (LCIS) lesions for case 33. The x-axis is ordered by chromosome, and the y-axis is the log ratio, representing the allele count, with areas of gains and loss represented by blue and red lines, respectively. Similar gains and losses were observed in both ILC and LCIS lesions
Fig. 2
Fig. 2
Copy number comparisons for case 31. Plots show distinct copy number changes for case 31, except for the ubiquitous 1q gains and 16q losses seen in most lobular carcinoma in situ (LCIS) lesions
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