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

'[Oxford Nanopore] adaptive sampling sequencing is suitable for the analysis of germline alterations, improves characterisation of large-scale rearrangements, and detects single nucleotide variations 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

Authors: Sandy Chevrier, Corentin Richard, Marie Mille, Denis Bertrand, Romain Boidot