Print Email Facebook Twitter Lack of Genomic Heterogeneity at High-Resolution aCGH between Primary Breast Cancers and Their Paired Lymph Node Metastases Title Lack of Genomic Heterogeneity at High-Resolution aCGH between Primary Breast Cancers and Their Paired Lymph Node Metastases Author Vollebergh, M.A. Klijn, C. Schouten, P.C. Wesseling, J. Israeli, D. Ylstra, B. Wessels, L.F.A. Jonkers, J. Linn, S.C. Faculty Electrical Engineering, Mathematics and Computer Science Department Intelligent Systems Date 2014-08-01 Abstract Lymph-node metastasis (LNM) predict high recurrence rates in breast cancer patients. Systemic treatment aims to eliminate (micro)metastatic cells. However decisions regarding systemic treatment depend largely on clinical and molecular characteristics of primary tumours. It remains, however, unclear to what extent metastases resemble the cognate primary breast tumours, especially on a genomic level, and as such will be eradicated by the systemic therapy chosen. In this study we used high-resolution aCGH to investigate DNA copy number differences between primary breast cancers and their paired LNMs. To date, no recurrent LNM-specific genomic aberrations have been identified using array comparative genomic hybridization (aCGH) analysis. In our study we employ a high-resolution platform and we stratify on different breast cancer subtypes, both aspects that might have underpowered previously performed studies.To test the possibility that genomic instability in triple-negative breast cancers (TNBCs) might cause increased random and potentially also recurrent copy number aberrations (CNAs) in their LNMs, we studied 10 primary TNBC-LNM pairs and 10 ER-positive (ER+) pairs and verified our findings adding additionally 5 TNBC-LNM and 22 ER+-LNM pairs. We found that all LNMs clustered nearest to their matched tumour except for two cases, of which one was due to the presence of two distinct histological components in one tumour. We found no significantly altered CNAs between tumour and their LNMs in the entire group or in the subgroups. Within the TNBC subgroup, no absolute increase in CNAs was found in the LNMs compared to their primary tumours, suggesting that increased genomic instability does not lead to more CNAs in LNMs. Our findings suggest a high clonal relationship between primary breast tumours and its LNMs, at least prior to treatment, and support the use of primary tumour characteristics to guide adjuvant systemic chemotherapy in breast cancer patients. To reference this document use: http://resolver.tudelft.nl/uuid:d391cd7e-fe04-47cf-927f-65b132ad8530 DOI https://doi.org/10.1371/journal.pone.0103177 Publisher Public Library of Science ISSN 1932-6203 Source PLoS ONE, 9 (8), 2014 Part of collection Institutional Repository Document type journal article Rights © 2014 The Author(s)This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Files PDF Wessels_2014.pdf 4.69 MB Close viewer /islandora/object/uuid:d391cd7e-fe04-47cf-927f-65b132ad8530/datastream/OBJ/view