Mutations detected in <i>DDB1, MLL</i> and <i>LMO2</i>.

<p><b>A</b>: Sample 36 harbored an 11q UPD as indicated by the blue bar below the chromosome 11 ideogram. We found two somatic mutations in <i>DDB1</i> and <i>CBL</i>. As can be seen in the Sanger sequencing traces, both mutations are homozygous due to amplification by the UPD. <b>B</b>: In sample 50 a tandem duplication in <i>MLL</i> exon 3 was detected. The top graph shows whole exome coverage data across <i>MLL</i> exon 3. The data is plotted as the log₂ ratio of the normalized exome sequencing coverage in the patient sample divided by the median normalized coverage of 8 independent control samples at each genomic position (X-axis). The position of the duplication is indicated by the red bar. Sanger sequencing confirmed an in-frame tandem duplication of 171 amino acids as shown at the bottom. <b>C</b>: A common deleted region on chromosome 11p targets <i>LMO2</i>. All deletions in the analyzed cohort that span the <i>LMO2</i> locus are depicted next to the chromosome 11 ideogram. Red bars indicate deletions, green bars indicate gains. In sample 42, which harbored a deletion spanning the LMO2 locus, we also detected a point mutation in <i>LMO2</i>. The middle section shows a signal intensity plot measuring copy number from Affymetrix microarrays. The plot depicts signal intensity (log₂ scale) differences between the patient and a healthy control pool for each probe (as implemented in the Affymetrix Genotyping Console software). The deletion in sample 42 can be seen as the deviation from 0 for all probes in the deleted genomic region (X-axis). The point mutation in <i>LMO2</i> as identified by Sanger sequencing is depicted at the bottom of panel C. <b>A</b>, <b>B</b> and <b>C</b>: Depicted are the genomic (letters) as well as the respective amino acid (box chains) sequences. Numbers above the boxes indicate amino acid positions in the proteins. Amino acids substituted in the patient samples are indicated by red boxes. The red circle indicates a splice site mutation. Reference and mutant sequences are shown. The arrows indicate the site of mutations below the Sanger sequencing traces.