Figure 4.
Somatic RUNX1 deletion and novel transcript. (A) CNV BedGraphs were generated by an in-house algorithm from the WES data for the germ line, diagnosis, and MBC samples of patient 3. The germ line gray central horizontal line indicates 2 copies of each gene. Extended red bars below the central line indicate a deletion of RUNX1 exons 3 to 7 at diagnosis and MBC. The extended black bars above the central line at MBC indicate chromosome 21 gain. (B) The RUNX1 deletion was confirmed by the CytoScan HD Array, where additional intronic markers revealed the full extent of the deletion. The genomic region is shown using the Affymetrix Chromosome Analysis Suite for the diagnosis and MBC samples. Red boxes represent the deletion, and blue boxes at MBC confirm the gain. (C) The deletion generated a novel in-frame RUNX1 exon 2 to 8 transcript. The splice junction tracks visualized in the Integrative Genomics Viewer are shown for a representative sample analyzed by RNA-Seq with normal RUNX1 splicing and the diagnosis and MBC samples of patient 3 with atypical RUNX1 exon 2 to 8 splicing. Arcs represent splice junctions that connect exons. Junctions from the minus strand are colored blue and extend below the center line. The arrowheads indicate the location of the genomic deletion breakpoints. RefSeq transcripts are shown at the bottom. (D) Sashimi plots of the diagnosis and MBC samples generated from the RUNX1 RNA-Seq splice junction track, which allows visualization of the novel splice generated by the deletion. Only the junctions that overlap RUNX1 RefSeq transcript ID NM_001754 exon 2 are shown. (E) The predicted novel isoform excludes the Runt DNA binding domain. (F) The stranded RNA-Seq protocol enabled sequencing of intron-retaining precursor RNA and genomic breakpoint detection. The intronic breakpoints were identified by RNA-Seq of the corresponding RNA samples at chr21:36392146 in intron 2 and chr21:36201259 in intron 7 (hg19). The genomic deletion junction was polymerase chain reaction amplified and Sanger sequenced, which confirmed a 190 888 base deletion.

Somatic RUNX1 deletion and novel transcript. (A) CNV BedGraphs were generated by an in-house algorithm from the WES data for the germ line, diagnosis, and MBC samples of patient 3. The germ line gray central horizontal line indicates 2 copies of each gene. Extended red bars below the central line indicate a deletion of RUNX1 exons 3 to 7 at diagnosis and MBC. The extended black bars above the central line at MBC indicate chromosome 21 gain. (B) The RUNX1 deletion was confirmed by the CytoScan HD Array, where additional intronic markers revealed the full extent of the deletion. The genomic region is shown using the Affymetrix Chromosome Analysis Suite for the diagnosis and MBC samples. Red boxes represent the deletion, and blue boxes at MBC confirm the gain. (C) The deletion generated a novel in-frame RUNX1 exon 2 to 8 transcript. The splice junction tracks visualized in the Integrative Genomics Viewer are shown for a representative sample analyzed by RNA-Seq with normal RUNX1 splicing and the diagnosis and MBC samples of patient 3 with atypical RUNX1 exon 2 to 8 splicing. Arcs represent splice junctions that connect exons. Junctions from the minus strand are colored blue and extend below the center line. The arrowheads indicate the location of the genomic deletion breakpoints. RefSeq transcripts are shown at the bottom. (D) Sashimi plots of the diagnosis and MBC samples generated from the RUNX1 RNA-Seq splice junction track, which allows visualization of the novel splice generated by the deletion. Only the junctions that overlap RUNX1 RefSeq transcript ID NM_001754 exon 2 are shown. (E) The predicted novel isoform excludes the Runt DNA binding domain. (F) The stranded RNA-Seq protocol enabled sequencing of intron-retaining precursor RNA and genomic breakpoint detection. The intronic breakpoints were identified by RNA-Seq of the corresponding RNA samples at chr21:36392146 in intron 2 and chr21:36201259 in intron 7 (hg19). The genomic deletion junction was polymerase chain reaction amplified and Sanger sequenced, which confirmed a 190 888 base deletion.

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