Evaluation of high-throughput genomic assays for the Fc gamma receptor locus

Hargreaves, C. E., Iriyama, C., Rose-Zerilli, M. J. J., Nagelkerke, S. Q., Hussain, K., Ganderton, R., Lee, C., Machado, L., Hollox, E. J., Parker, H., Latham, K. V., Kuijpers, T. W., Potter, K. N., Coupland, S. E., Davies, A., Stackpole, M., Oates, M., Pettitt, A. R., Glennie, M. J., Cragg, M. S. and Strefford, J. C. (2015) Evaluation of high-throughput genomic assays for the Fc gamma receptor locus. PLoS ONE. 10(11), pp. 1-13. 1932-6203.

Hargreaves_etal_PLOS_2015_Evaluation_of_High_Throughput_Genomic_Assays_for_the_Fc_Gamma_Receptor_Locus (1MB)

Item Type:	Article
Abstract:	Cancer immunotherapy has been revolutionised by the use of monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (FcγRs). The low-affinity FcγR genes are highly homologous, map to a complex locus at 1p23 and harbour single nucleotide polymorphisms (SNPs) and copy number variation (CNV) that can impact on receptor function and response to therapeutic mAbs. This complexity can hinder accurate characterisation of the locus. We therefore evaluated and optimised a suite of assays for the genomic analysis of the FcγR locus amenable to peripheral blood mononuclear cells and formalin-fixed paraffin-embedded (FFPE) material that can be employed in a high-throughput manner. Assessment of TaqMan genotyping for FCGR2A-131H/R, FCGR3A-158F/V and FCGR2B-232I/T SNPs demonstrated the need for additional methods to discriminate genotypes for the FCGR3A-158F/V and FCGR2B-232I/T SNPs due to sequence homology and CNV in the region. A multiplex ligation-dependent probe amplification assay provided high quality SNP and CNV data in PBMC cases, but there was greater data variability in FFPE material in a manner that was predicted by the BIOMED-2 multiplex PCR protocol. In conclusion, we have evaluated a suite of assays for the genomic analysis of the FcγR locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of FcγR genetics in predicting response to antibody therapeutics.
Uncontrolled Keywords:	/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Creators:	Hargreaves, Chantal E, Iriyama, Chisako, Rose-Zerilli, Matthew J J, Nagelkerke, Sietse Q, Hussain, Khiyam, Ganderton, Rosalind, Lee, Charlotte, Machado, Lee, Hollox, Edward J, Parker, Helen, Latham, Kate V, Kuijpers, Taco W, Potter, Kathleen N, Coupland, Sarah E, Davies, Andrew, Stackpole, Micheal, Oates, Melanie, Pettitt, Andrew R, Glennie, Martin J, Cragg, Mark S and Strefford, Jonathan C
Faculties, Divisions and Institutes:	Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences Research Centres > Centre for Physical Activity and Life Sciences
Date:	6 November 2015
Date Type:	Publication
Page Range:	pp. 1-13
Journal or Publication Title:	PLoS ONE
Volume:	10
Number:	11
Number of Pages:	13
Language:	English
DOI:	https://doi.org/10.1371/journal.pone.0142379
ISSN:	1932-6203
Status:	Published / Disseminated
Refereed:	Yes
Related URLs:	https://pure.northampton.ac.uk/en/public...
URI:	http://nectar.northampton.ac.uk/id/eprint/13216

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