TY - JOUR
T1 - Lobular carcinomas in situ display intralesion genetic heterogeneity and clonal evolution in the progression to invasive lobular carcinoma
AU - Lee, Ju Youn
AU - Schizas, Michail
AU - Geyer, Felipe C.
AU - Selenica, Pier
AU - Piscuoglio, Salvatore
AU - Sakr, Rita A.
AU - Ng, Charlotte K.Y.
AU - Scarpa Carniello, Jose V.
AU - Towers, Russell
AU - Giri, Dilip D.
AU - de Andrade, Victor P.
AU - Papanastasiou, Anastasios D.
AU - Viale, Agnes
AU - Harris, Reuben S.
AU - Solit, David B.
AU - Weigelt, Britta
AU - Reis-Filho, Jorge S.
AU - King, Tari A.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2019/1/15
Y1 - 2019/1/15
N2 - Purpose: Lobular carcinoma in situ (LCIS) is a preinvasive mutations present in 81% of the lesions. Forty-two percent lesion of the breast. We sought to define its genomic landscape, (18/43) of LCIS were found to be clonally related to synchro-whether intralesion genetic heterogeneity is present in LCIS, nous DCIS and/or ILCs, with clonal evolutionary patterns and the clonal relatedness between LCIS and invasive breast indicative of clonal selection and/or parallel/branched pro-cancers. gression. Intralesion genetic heterogeneity was higher among Experimental Design: We reanalyzed whole-exome LCIS clonally related to DCIS/ILC than in those nonclonally sequencing (WES) data and performed a targeted amplicon related to DCIS/ILC. A shift from aging to APOBEC-related sequencing validation of mutations identified in 43 LCIS and mutational processes was observed in the progression from 27 synchronous more clinically advanced lesions from 24 LCIS to DCIS and/or ILC in a subset of cases. patients [9 ductal carcinomas in situ (DCIS), 13 invasive Conclusions: Our findings support the contention that lobular carcinomas (ILC), and 5 invasive ductal carcinomas LCIS has a repertoire of somatic genetic alterations similar to (IDC)]. Somatic genetic alterations, mutational signatures, that of ILCs, and likely constitutes a nonobligate precursor of clonal composition, and phylogenetic trees were defined using breast cancer. Intralesion genetic heterogeneity is observed in validated computational methods. LCIS and should be considered in studies aiming to develop Results: WES of 43 LCIS lesions revealed a genomic profile biomarkers of progression from LCIS to more advanced similar to that previously reported for ILCs, with CDH1 lesions.
AB - Purpose: Lobular carcinoma in situ (LCIS) is a preinvasive mutations present in 81% of the lesions. Forty-two percent lesion of the breast. We sought to define its genomic landscape, (18/43) of LCIS were found to be clonally related to synchro-whether intralesion genetic heterogeneity is present in LCIS, nous DCIS and/or ILCs, with clonal evolutionary patterns and the clonal relatedness between LCIS and invasive breast indicative of clonal selection and/or parallel/branched pro-cancers. gression. Intralesion genetic heterogeneity was higher among Experimental Design: We reanalyzed whole-exome LCIS clonally related to DCIS/ILC than in those nonclonally sequencing (WES) data and performed a targeted amplicon related to DCIS/ILC. A shift from aging to APOBEC-related sequencing validation of mutations identified in 43 LCIS and mutational processes was observed in the progression from 27 synchronous more clinically advanced lesions from 24 LCIS to DCIS and/or ILC in a subset of cases. patients [9 ductal carcinomas in situ (DCIS), 13 invasive Conclusions: Our findings support the contention that lobular carcinomas (ILC), and 5 invasive ductal carcinomas LCIS has a repertoire of somatic genetic alterations similar to (IDC)]. Somatic genetic alterations, mutational signatures, that of ILCs, and likely constitutes a nonobligate precursor of clonal composition, and phylogenetic trees were defined using breast cancer. Intralesion genetic heterogeneity is observed in validated computational methods. LCIS and should be considered in studies aiming to develop Results: WES of 43 LCIS lesions revealed a genomic profile biomarkers of progression from LCIS to more advanced similar to that previously reported for ILCs, with CDH1 lesions.
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U2 - 10.1158/1078-0432.CCR-18-1103
DO - 10.1158/1078-0432.CCR-18-1103
M3 - Article
C2 - 30185420
AN - SCOPUS:85060045931
SN - 1078-0432
VL - 25
SP - 674
EP - 686
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -
