Schouten, P. C., Grigoriadis, A., Kuilman, T., Mirza, H., Watkins, J. A., Cooke, S. A., van Dyk, E., Severson, T. M., Rueda, O. M., Hoogstraat, M., Verhagen, C. V. M., Natrajan, R., Chin, S. F., Lips, E. H., Kruizinga, J., Velds, A., Nieuwland, M., Kerkhoven, R. M., Krijgsman, O., Vens, C., Peeper, D., Nederlof, P. M., Caldas, C., Tutt, A. N., Wessels, L. F., Linn, S. C. (2015) Robust BRCA1-like classification of copy number profiles of samples repeated across different datasets and platforms. MOLECULAR ONCOLOGY, 9 (7). pp. 1274-1286. ISSN 1574-7891

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Abstract

Breast cancers with BRCA1 germline mutation have a characteristic DNA copy number (CN) pattern. We developed a test that assigns CN profiles to be 'BRCA1-like' or 'non-BRCA1-like', which refers to resembling a BRCA1-mutated tumor or resembling a tumor without a BRCA1 mutation, respectively. Approximately one third of the BRCA1-like breast cancers have a BRCA1 mutation, one third has hypermethylation of the BRCA1 promoter and one third has an unknown reason for being BRCA1-like. This classification is indicative of patients' response to high dose alkylating and platinum containing chemotherapy regimens, which targets the inability of BRCA1 deficient cells to repair DNA double strand breaks. We investigated whether this classification can be reliably obtained with next generation sequencing and copy number platforms other than the bacterial artificial chromosome (BAC) array Comparative Genomic Hybridization (aCGH) on which it was originally developed. We investigated samples from 230 breast cancer patients for which a CN profile had been generated on two to five platforms, comprising low coverage CN sequencing, CN extraction from targeted sequencing panels (CopywriteR), Affymetrix SNP6.0, 135K/720K oligonucleotide aCGH, Affymetrix Oncoscan FFPE (MIP) technology, 3K BAC and 32K BAC aCGH. Pairwise comparison of genomic position-mapped profiles from the original aCGH platform and other platforms revealed concordance. For most cases, biological differences between samples exceeded the differences between platforms within one sample. We observed the same classification across different platforms in over 80% of the patients and kappa values of at least 0.36. Differential classification could be attributed to CN profiles that were not strongly associated to one class. In conclusion, we have shown that the genomic regions that define our BRCA1-like classifier are robustly measured by different CN profiling technologies, providing the possibility to retro- and prospectively investigate BRCA1-like classification across a wide range of CN platforms. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.

Item Type:	Article
Authors (ICR Faculty only):	Natrajan, Rachael
All Authors:	Schouten, P. C., Grigoriadis, A., Kuilman, T., Mirza, H., Watkins, J. A., Cooke, S. A., van Dyk, E., Severson, T. M., Rueda, O. M., Hoogstraat, M., Verhagen, C. V. M., Natrajan, R., Chin, S. F., Lips, E. H., Kruizinga, J., Velds, A., Nieuwland, M., Kerkhoven, R. M., Krijgsman, O., Vens, C., Peeper, D., Nederlof, P. M., Caldas, C., Tutt, A. N., Wessels, L. F., Linn, S. C.
Additional Information:	ISI Document Delivery No.: CP4XB Times Cited: 0 Cited Reference Count: 45 Schouten, Philip C. Grigoriadis, Anita Kuilman, Thomas Mirza, Hasan Watkins, Johnathan A. Cooke, Saskia A. van Dyk, Ewald Severson, Tesa M. Rueda, Oscar M. Hoogstraat, Marlous Verhagen, Caroline V. M. Natrajan, Rachael Chin, Suet-Feung Lips, Esther H. Kruizinga, Janneke Velds, Arno Nieuwland, Marja Kerkhoven, Ron M. Krijgsman, Oscar Vens, Conchita Peeper, Daniel Nederlof, Petra M. Caldas, Carlos Tutt, Andrew N. Wessels, Lodewyk F. Linn, Sabine C. Roche Life Science; Life Sciences Center Amsterdam (LSCA) Validation fund; FP7 Collaborative Project "RATHER" This work was supported by an unrestricted research grant from Roche Life Science to translate the BRCA1-like classifier to a next generation sequencing platform, a grant from the Life Sciences Center Amsterdam (LSCA) Validation fund and the FP7 Collaborative Project "RATHER" (www.ratherproject.com). 0 ELSEVIER SCI LTD OXFORD MOL ONCOL
Uncontrolled Keywords:	BRCA1 Breast cancer Classification Copy number aberration profiles COMPARATIVE GENOMIC HYBRIDIZATION BREAST-CANCER ARRAY-CGH PROMOTER HYPERMETHYLATION TUMORS CHEMOTHERAPY CARCINOMAS SEGMENTATION DEFICIENCY GENES
Research teams:	ICR divisions > Breast Cancer Research > Functional Genomics
Depositing User:	Barry Jenkins
Date Deposited:	17 Sep 2015 12:38
Last Modified:	18 Sep 2015 11:47
URI:	http://publications.icr.ac.uk/id/eprint/14367

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