The influence of FCGR2A and FCGR3A polymorphisms on the survival of patients with recurrent or metastatic squamous cell head and neck cancer treated with cetuximab (vol 18, pg 474, 2018)
PHARMACOGENOMICS JOURNAL
Authors: Magnes, T.; Melchardt, T.; Hufnagl, C.; Weiss, L.; Mittermair, C.; Neureiter, D.; Klieser, E.; Rinnerthaler, G.; Roesch, S.; Gaggl, A.; Greil, R.; Egle, A.
Abstract
In the abstract and in other parts of the manuscript the authors wrote that the mutation rs396991 causes a valine (V) to phenylalanine (F) substitution at position 157. However, the correct codon number is 158. These errors have not been fixed in the original Article.
Evaluation of High-Throughput Genomic Assays for the Fc Gamma Receptor Locus
PLOS ONE
Authors: Hargreaves, Chantal E.; Iriyama, Chisako; Rose-Zerilli, Matthew J. J.; Nagelkerke, Sietse Q.; Hussain, Khiyam; Ganderton, Rosalind; Lee, Charlotte; Machado, Lee R.; Hollox, Edward J.; Parker, Helen; Latham, Kate V.; Kuijpers, Taco W.; Potter, Kathleen N.; Coupland, Sarah E.; Davies, Andrew; Stackpole, Michael; Oates, Melanie; Pettitt, Andrew R.; Glennie, Martin J.; Cragg, Mark S.; Strefford, Jonathan C.
Abstract
Cancer immunotherapy has been revolutionised by the use monoclonal antibodies (mAb) that function through their interaction with Fc gamma receptors (Fc gamma Rs). The low-affinity Fc gamma R 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 Fc gamma R 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 Fc gamma R locus that are scalable for application in large clinical trials of mAb therapy. These assays will ultimately help establish the importance of Fc gamma R genetics in predicting response to antibody therapeutics.