Recurrent abnormalities in p53-related genes in peripheral T-cell lymphomas. (A) PCR using tumor-specific primers (supplemental Table 1) designed from aberrant mate-pair sequences from SR-786 indicating juxtaposition of POLR2A and WRAP53, situated on either side of TP53. (B) Partial results of Sanger sequencing (nucleotides in red) of the SR-786 amplicon from panel A spanning the POLR2A/WRAP53 breakpoints. (C) Count plot showing chr17p based on mate-pair data from TCL3, showing TP53 deletion. Each circle represents a 52-kb window (W, based on genomic coverage; see “Mate-pair data mapping and bioinformatic analysis”); the position along the y-axis represents the number of mate pairs mapping within each window. The horizontal red line represents the number of mate pairs expected for a copy-neutral locus based on normalization across the entire genome. The horizontal blue line represents the aberrant mate pairs, which map ∼ 174 kb apart (instead of the expected ∼ 5 kb based on the size selection used for mate-pair library preparation). (D) MLPA (see “Methods”) for ANKRD11 in cases without (TCL5, left) and with (TCL29, right) homozygous deletions. Numerals represent ratios of patient samples (blue peaks) to normal female controls (red peaks) for 2 probes (ANKR1 and ANKR12) to exon 1 of ANKRD11. The remaining gene probes are reference controls. (E) Metaphase CDKN2A/B FISH image from TCL29. Arrows point to centromeres of chromosomes 9 (CEP9; green signals). There is homozygous deletion of CDKN2A/B (absent red signals). For comparison, an interphase nucleus with 2 copies of the CDKN2A/B gene region is seen at bottom right (arrowhead). (F) Summary of abnormalities in p53-related genes in 21 sequenced PTCLs, with status of translocations involving DUSP22-IRF4 or ALK. There were 16 patient samples (“TCL” identifiers) and 6 cell lines (SR-786, Karpas [K] 299, SU-DHL-1, FEPD, MAC1, and MAC2A). MAC1 and MAC2A were considered together as they were derived from the same patient.