HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study

Abstract Breast cancer treatment depends on human epidermal growth factor receptor-2 (HER2) status, which is often determined using dual probe fluorescence in situ hybridisation (FISH). Hereby, also loss and gain of the centromere of chromosome 17 (CEP17) can be observed (HER2 is located on chromoso...

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Autores principales:	Altuna Halilovic, Dagmar I. Verweij, Annet Simons, Marian J. P. L. Stevens-Kroef, Susan Vermeulen, Janet Elsink, Bastiaan B. J. Tops, Irene Otte-Höller, Jeroen A. W. M. van der Laak, Carlijn van de Water, Oliver B. A. Boelens, Margrethe S. Schlooz-Vries, Jeroen R. Dijkstra, Iris D. Nagtegaal, Jolien Tol, Patricia H. J. van Cleef, Paul N. Span, Peter Bult
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eccb0d74ba084146a4c3d5d34a19dea5
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spelling	oai:doaj.org-article:eccb0d74ba084146a4c3d5d34a19dea52021-12-02T15:09:53ZHER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study10.1038/s41598-019-48212-22045-2322https://doaj.org/article/eccb0d74ba084146a4c3d5d34a19dea52019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48212-2https://doaj.org/toc/2045-2322Abstract Breast cancer treatment depends on human epidermal growth factor receptor-2 (HER2) status, which is often determined using dual probe fluorescence in situ hybridisation (FISH). Hereby, also loss and gain of the centromere of chromosome 17 (CEP17) can be observed (HER2 is located on chromosome 17). CEP17 gain can lead to difficulty in interpretation of HER2 status, since this might represent true polysomy. With this study we investigated whether isolated polysomy is present and how this effects HER2 status in six breast cancer cell lines and 97 breast cancer cases, using HER2 FISH and immunohistochemistry, DNA ploidy assessment and multiplex ligation dependent probe amplification. We observed no isolated polysomy of chromosome 17 in any cell line. However, FISH analysis did show CEP17 gain in five of six cell lines, which reflected gains of the whole chromosome in metaphase spreads and aneuploidy with gain of multiple chromosomes in all these cases. In patients’ samples, gain of CEP17 indeed correlated with aneuploidy of the tumour (91.1%; p < 0.001). Our results indicate that CEP17 gain is not due to isolated polysomy, but rather due to widespread aneuploidy with gain of multiple chromosomes. As aneuploidy is associated with poor clinical outcome, irrespective of tumour grade, this could improve future therapeutic decision making.Altuna HalilovicDagmar I. VerweijAnnet SimonsMarian J. P. L. Stevens-KroefSusan VermeulenJanet ElsinkBastiaan B. J. TopsIrene Otte-HöllerJeroen A. W. M. van der LaakCarlijn van de WaterOliver B. A. BoelensMargrethe S. Schlooz-VriesJeroen R. DijkstraIris D. NagtegaalJolien TolPatricia H. J. van CleefPaul N. SpanPeter BultNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Altuna Halilovic Dagmar I. Verweij Annet Simons Marian J. P. L. Stevens-Kroef Susan Vermeulen Janet Elsink Bastiaan B. J. Tops Irene Otte-Höller Jeroen A. W. M. van der Laak Carlijn van de Water Oliver B. A. Boelens Margrethe S. Schlooz-Vries Jeroen R. Dijkstra Iris D. Nagtegaal Jolien Tol Patricia H. J. van Cleef Paul N. Span Peter Bult HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study
description	Abstract Breast cancer treatment depends on human epidermal growth factor receptor-2 (HER2) status, which is often determined using dual probe fluorescence in situ hybridisation (FISH). Hereby, also loss and gain of the centromere of chromosome 17 (CEP17) can be observed (HER2 is located on chromosome 17). CEP17 gain can lead to difficulty in interpretation of HER2 status, since this might represent true polysomy. With this study we investigated whether isolated polysomy is present and how this effects HER2 status in six breast cancer cell lines and 97 breast cancer cases, using HER2 FISH and immunohistochemistry, DNA ploidy assessment and multiplex ligation dependent probe amplification. We observed no isolated polysomy of chromosome 17 in any cell line. However, FISH analysis did show CEP17 gain in five of six cell lines, which reflected gains of the whole chromosome in metaphase spreads and aneuploidy with gain of multiple chromosomes in all these cases. In patients’ samples, gain of CEP17 indeed correlated with aneuploidy of the tumour (91.1%; p < 0.001). Our results indicate that CEP17 gain is not due to isolated polysomy, but rather due to widespread aneuploidy with gain of multiple chromosomes. As aneuploidy is associated with poor clinical outcome, irrespective of tumour grade, this could improve future therapeutic decision making.
format	article
author	Altuna Halilovic Dagmar I. Verweij Annet Simons Marian J. P. L. Stevens-Kroef Susan Vermeulen Janet Elsink Bastiaan B. J. Tops Irene Otte-Höller Jeroen A. W. M. van der Laak Carlijn van de Water Oliver B. A. Boelens Margrethe S. Schlooz-Vries Jeroen R. Dijkstra Iris D. Nagtegaal Jolien Tol Patricia H. J. van Cleef Paul N. Span Peter Bult
author_facet	Altuna Halilovic Dagmar I. Verweij Annet Simons Marian J. P. L. Stevens-Kroef Susan Vermeulen Janet Elsink Bastiaan B. J. Tops Irene Otte-Höller Jeroen A. W. M. van der Laak Carlijn van de Water Oliver B. A. Boelens Margrethe S. Schlooz-Vries Jeroen R. Dijkstra Iris D. Nagtegaal Jolien Tol Patricia H. J. van Cleef Paul N. Span Peter Bult
author_sort	Altuna Halilovic
title	HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study
title_short	HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study
title_full	HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study
title_fullStr	HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study
title_full_unstemmed	HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study
title_sort	her2, chromosome 17 polysomy and dna ploidy status in breast cancer; a translational study
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/eccb0d74ba084146a4c3d5d34a19dea5
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HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study

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