Identification of a new class of local copy number aberrations in lung cancer genomes using PromethION

Yutaka Suzuki (University of Tokyo) gave a lightning talk discussing his team's use of nanopore technology in cancer genome sequencing to identify copy number variations. Whole-genome, long-read sequencing of lung cancer samples was performed using the high-throughput PromethION device; Yutaka pointed out that two PromethION Flow Cells enabled the same depth-of-coverage as if he had used ~20-30 MinION Flow Cells.

Analysis enabled the detection of both larger mutations and point mutations. Alongside common mutations, a novel structural variant were identified in the gene STKII: a cancerous local copy-number lesion (CLCL); Yutaka decribed how the complexity of this structural variant meant that it would not be possible to resolve with short reads. This was associated with abnormal transcription of STKII, although the promoter remained intact, so it was still expressed. Biological validation was achieved via western blotting. Yutaka noted that complex structural variants are quite frequent in lung cancer, especially in functionally important key genes. A similar analysis of 9 clinical samples found that such mutations were quite frequent, and indicated that the mutations previously identified were not a result of cell line artefacts. Yutaka again described how these would have been missed by short reads, which could explain an instance in which aberrant transcripts were observed without identification of the genomic mutation.