47. Genomic characterization of the T-ALL cell line CCRF-CEM using optical genome mapping and nanopore sequencing

Human Cancer cell lines provide a valuable model for detecting genomic alterations and chromosomal aberrations to identify and validate new diagnostic or therapeutic targets. Here, we recharacterize the T-cell acute lymphocytic leukemia (T-ALL) cell line CCRF-CEM (ATCC #CCL-119) using karyotyping, FISH, aCGH, and emerging genomic technologies of optical genome mapping (OGM) and nanopore long-read sequencing (LRS). Consistent with the previous literature, karyotyping and FISH indicated a modal number of 47, with t(8;9)(p12;p24) and trisomy 20 in analyzed metaphases. ACGH confirmed trisomy 20 apparent in the karyotype but also showed both an unbalanced der(5)t(5;14)(q35.2;q32.2) translocation, independently confirmed by FISH, and a 226-kb deletion at 10q23.31 containing the tumor suppressor gene PTEN, concordant with existing literature. Saphyr-based OGM analysis confirmed the aCGH data; however, OGM analysis additionally identified monosomy X (copy number fraction 1.579), which could arise from a subclonal population as previously reported, and the breakpoint at 8p11.21 as the true region of the balanced translocation. Strikingly, OGM also identified a novel likely pathogenic cryptic 81.9-kb deletion at 1p33 overlapping the STIL gene (80X coverage). Deletions of STIL are known to occur in T-cell leukemias although this aberration has not been described in the CCRF-CEM cell line. We are currently in the process of analyzing LRS data to validate OGM findings and determine precise deletion breakpoints. Collectively, our data have identified a novel chromosomal aberration in the CCRF-CEM cell line providing a framework for further functional characterization.