TCR and BCR loci copy number aberration detection for FFPE tissues using MIP-based assay

The classification of haematolymphoid neoplasms has important clinical implications, yet current methods to determine cell lineage on formalin-fixed paraffin-embedded (FFPE) tissues are unsatisfactory, especially for neoplasms of NK- and T-cell lineages. Herein, we performed copy number analysis using the MIP platform on 86 cases, including T-, NK- and B-cell lymphomas, malignant cell lines and normal lymphocyte subsets. We demonstrate that the loss of T- and B-cell receptor gene loci correlates with cell lineage. The overall sensitivity of the assay in our cohort was 91% and 78%, while the specificity was 84% and 93%, for the corresponding antigen receptors in T- and B-cell samples, respectively. Fluorescence in situ hybridization showed no detectable translocation or deletion of the TCRA locus in samples showing loss of TCRA. Compared to PCR-based gene arrangement assay for lineage assignment, the MIP assay showed good reliability on FFPE samples, including cases more than 10 years old. In conclusion, the detection of the loss of the antigen receptor gene loci using the MIP array is a novel genetic marker of lymphoid cell lineage and a potentially valuable tool in the diagnosis and classification of lymphoid neoplasms especially of T- and NK-cell origin. Comparison of T-, B- and NK-cells of diverse diseases with reference.