edoc

Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma

Lee, Ju Youn and Schizas, Michail and Geyer, Felipe C. and Selenica, Pier and Piscuoglio, Salvatore and Sakr, Rita A. and Ng, Charlotte K. Y. and Carniello, Jose V. Scarpa and Towers, Russell and Giri, Dilip D. and de Andrade, Victor P. and Papanastasiou, Anastasios D. and Viale, Agnes and Harris, Reuben S. and Solit, David B. and Weigelt, Britta and Reis-Filho, Jorge S. and King, Tari A.. (2018) Lobular Carcinomas In Situ Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma. Clinical cancer research, 25 (2). pp. 674-686.

[img] PDF - Accepted Version
Restricted to Repository staff only until 16 January 2020.

3451Kb

Official URL: https://edoc.unibas.ch/68167/

Downloads: Statistics Overview

Abstract

Purpose:; Lobular carcinoma; in situ; (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers.; Experimental Design:; We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas; in situ; (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)]. Somatic genetic alterations, mutational signatures, clonal composition, and phylogenetic trees were defined using validated computational methods.; Results:; WES of 43 LCIS lesions revealed a genomic profile similar to that previously reported for ILCs, with; CDH1; mutations present in 81% of the lesions. Forty-two percent (18/43) of LCIS were found to be clonally related to synchronous DCIS and/or ILCs, with clonal evolutionary patterns indicative of clonal selection and/or parallel/branched progression. Intralesion genetic heterogeneity was higher among LCIS clonally related to DCIS/ILC than in those nonclonally related to DCIS/ILC. A shift from aging to APOBEC-related mutational processes was observed in the progression from LCIS to DCIS and/or ILC in a subset of cases.; Conclusions:; Our findings support the contention that LCIS has a repertoire of somatic genetic alterations similar to that of ILCs, and likely constitutes a nonobligate precursor of breast cancer. Intralesion genetic heterogeneity is observed in LCIS and should be considered in studies aiming to develop biomarkers of progression from LCIS to more advanced lesions.
Faculties and Departments:03 Faculty of Medicine
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Piscuoglio, Salvatore
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for Cancer Research
ISSN:1078-0432
e-ISSN:1557-3265
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:29 Jan 2019 11:16
Deposited On:29 Jan 2019 11:09

Repository Staff Only: item control page