Nanopore adaptive sampling accurately detects nucleotide variants and improves the characterisation of large-scale rearrangement for the diagnosis of cancer predisposition

Chevrier et al. used Oxford Nanopore adaptive sampling as an alternative method to multiplex ligation-dependent probe amplification (MLPA) for studying genes associated with cancer predisposition. They detected known and novel variants, even at low coverage, and characterised large-scale rearrangements, noting higher resolution with Oxford Nanopore than MLPA. Therefore, Oxford Nanopore sequencing could potentially be an accurate alternative method for early cancer detection in the future.

Key points:

• Adaptive sampling enriched 152 cancer predisposition genes in blood samples from individuals with hereditary solid tumour cancers

• Using Oxford Nanopore, Chevrier et al. detected known and novel variants, including a duplication of two exons and a deletion carrying over five different genes

• All large-scale rearrangements were detected in the 30 germline samples, matching MLPA results

• Oxford Nanopore sequencing characterised the exact start, stop, and size of large-scale rearrangements, offering better resolution than MLPA

• The authors identified novel intronic variants that could impact splicing

• Oxford Nanopore sequencing offered improved detection of structural variants (SVs) and single nucleotide variants (SNVs) even at low coverage

Watch the lead author, Romain Boidot, discuss this research at London Calling 2023.

Sample type: human blood

Kit: Ligation Sequencing Kit