Fig. 2

Co-occurrence of 12q CN-LOH, amplification of chromosome 21 and deletion of SH2B3. a On the left SNP 6.0 genotype profiles show the relative signal intensity of the B allele probes for chromosome 12. Normal genomic regions are characterized by three levels of intensity corresponding to the AA, AB and BB genotypes and regions of CN-LOH by loss of the AB genotype. Arrows mark the proximal boundary of CN-LOH which were terminal in each case. To the right are shown patient IDs and chromosome 21 log 2 CN profiles, black lines mark the mean signal intensity for a CN of 2. All patients showed evidence for structural amplification of chromosome 21, as indicated, six abnormalities were defined as iAMP21. b Heat maps of CN for a region of 12q showing clonal deletion in two patients with 12q CN-LOH. Both deletions were bi-allelic with the smaller of the two confined to exons of SH2B3 and ATXN2. c Suggesting they target a common underlying genomic abnormality, allelotype and CN heat maps for a presentation sample from patient 78 (P 78) were consistent with the presence of competing sub-clones carrying 12q CN-LOH and a mono-allelic deletion that included the SH2B3/ATXN2 region. In a PDX derived from the same sample (PDX 78), CN-LOH was lost while the deletion became clonal. To the right a detailed view of dot-plots of SNP 6.0 CN within the deleted region, suggests the presence of a somatically acquired bi-allelic micro-deletion centred on exon 2 of SH2B3 in both patient and PDX samples but not the remission sample (R 78). Black lines indicate a copy number of 2. Arrows indicate the position of SH2B3 exon 2. d Sequence amplified from patient 78 using SH2B3 intron 1 and 2 primers that defines breakpoints for a 17.4 Kb deletion. e SNP6.0 CN heat maps of deletions that included the SH2B3 region found in three iAMP21 patients without CN-LOH 12q. In patient 61 the deletion is mono-allelic while in patients 3 and 72 nested deletions resulted in bi-allelic loss of SH2B3