In situ single cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2+ breast cancer

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In situ single cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2+ breast cancer

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Title: In situ single cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2+ breast cancer
Author: Janiszewska, Michalina; Liu, Lin; Almendro, Vanessa; Kuang, Yanan; Paweletz, Cloud; Sakr, Rita A.; Weigelt, Britta; Hanker, Ariella B.; Chandarlapaty, Sarat; King, Tari A.; Reis-Filho, Jorge S.; Arteaga, Carlos L.; Park, So Yeon; Michor, Franziska; Polyak, Kornelia

Note: Order does not necessarily reflect citation order of authors.

Citation: Janiszewska, M., L. Liu, V. Almendro, Y. Kuang, C. Paweletz, R. A. Sakr, B. Weigelt, et al. 2015. “In situ single cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2+ breast cancer.” Nature genetics 47 (10): 1212-1219. doi:10.1038/ng.3391. http://dx.doi.org/10.1038/ng.3391.
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Abstract: Detection of minor genetically distinct subpopulations within tumors is a key challenge in cancer genomics. Here we report STAR-FISH (Specific-To-Allele PCR – FISH), a novel method for the combined detection of single nucleotide and copy number alterations in single cells in intact archived tissues. Using this method, we assessed the clinical impact of changes in the frequency and topology of PIK3CA mutation and HER2/ERBB2 amplification within HER2+ breast cancer during neoadjuvant therapy. We found that the two genetic events are not always present within the same cell. Chemotherapy selects for PIK3CA mutant cells, a minor subpopulation in nearly all treatment-naïve samples, and modulates genetic diversity within tumors. Treatment-associated changes in spatial distribution of cellular genetic diversity correlated with poor long-term outcome following adjuvant trastuzumab therapy. Our findings support the use of in situ single-cell based methods in cancer genomics and imply that chemotherapy before HER2-targeted therapy may promote treatment resistance.
Published Version: doi:10.1038/ng.3391
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589505/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860200
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