Combination of Long-Read Sequencing and Hi-C Technology to Identify Chromoanagenesis Events in Cancer.

Structural variants are of major importance in cancer genetics. Especially when it comes to the detection of complex structural variants as in chromoanagenesis, detection tools like array-CGH, karyotyping, or even whole-genome sequencing do not provide the necessary resolution and/or accuracy. Here, we present a novel structural variant (SV) detection workflow that integrates genomic DNA (gDNA) long-read sequencing and Hi-C sequencing. With this workflow, high-confident SV calling at very high resolution can be archived. Applying it to a cohort of acute myeloid leukemia (AML) with a complex karyotype led to new insights about the actual complexity of chromoanagenesis and can enhance subsequent functional studies of the underlying pathomechanisms.