In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2908-2908
Abstract:
We previously studied synchronous Ductal Carcinomas in Situ (DCIS) and Invasive Ductal Carcinomas (IDC) using a novel approach of multiplexing FISH probes that allows us to simultaneously assess the copy numbers of up to 20 loci within intact nuclei providing new insights into tumor clonality and heterogeneity. A high degree of chromosomal instability already in DCIS, and frequently, but not always, a direct clonal evolution from DCIS to IDC was detected. We now ask whether this degree of instability is also present in DCIS that did not progress to IDC and are therefore analyzing FFPE material from 20 patients with either low-grade and high-grade DCIS who did not present with invasive breast carcinoma during their follow-up (5-10 years), in addition to 10 patients who presented with synchronous IDC. The multiplex FISH assay used targets five oncogenes (COX2, MYC, CCND1, HER2, ZNF217) and three tumor suppressor genes (DBC2, CDH1, TP53) frequently altered in breast carcinomas. To date, we have analyzed two paired cases of synchronous DCIS and IDC, DCIS-IDC 3 and 4, and three cases of DCIS without IDC, OP-DCIS 1, 4 and 5. The paired cases exhibited very similar aberration patterns for synchronous DCIS and IDC indicating the invasive carcinoma is closely related to the DCIS lesion. Specifically, the major clones in DCIS 3 (low-grade) and IDC 3 showed a diploid tumor cell population with a gain of COX2, and losses of DBC2, MYC, TP53, and HER2. Of note, the only difference observed was a gain of ZNF217 in the DCIS which was not seen in the major clone of the invasive carcinoma. The other paired case, DCIS 4 (high-grade) and IDC 4, showed major clones of triploid tumor cell populations with gains of COX2, CCND1 and MYC and losses of DBC2, CDH1, TP53 and ZNF217. The three DCIS cases without synchronous or subsequent IDC exhibited varying degrees of aberration and complexity patterns in their clonal populations. Case OP-DCIS 1, a high-grade DCIS, revealed a tetraploid cell population which showed a major clone with an amplification of CCND1 and a MYC gain combined with losses of DBC2, CDH1, TP53 and HER2. A low-grade DCIS, OP-DCIS 4, exhibited a diploid cell population with a major clone showing loss of CDH1 as the only aberration. The third case OP-DCIS 5 (low-grade DCIS) exhibited a diploid cell population with one major clone showing losses of CDH1, MYC, DBC2, TP53, HER2 and CCND1. Our preliminary observations show a tendency of diploid lesions with a predominance of loss patterns for low-grade DCIS, while high-grade DCIS seem to reveal higher ploidy with more complex gain and loss patterns. However, also low-grade DCIS with mainly loss patterns progress to invasive cancers as seen in case DCIS-IDC3. We expect that the analysis of the remaining cases will further elucidate the dynamics of DCIS lesions which will hopefully help to assess and stratify progression risk in patients with DCIS. Citation Format: Irianna Marie Torres, Leanora Hernandez, Jausheng Tzeng, Russell Schwartz, Alejandro Schaffer, Edward Gertz, Stephen Brower, Miguel Sanchez, Gert Auer, Kerstin Heselmeyer-Haddad, Ried Thomas. Single-cell genetic analysis of ductal carcinoma in situ with and without synchronous invasive breast cancer by multiplex FISH delineates specific patterns of tumor clonality and heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2908. doi:10.1158/1538-7445.AM2017-2908
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-2908
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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