Resolving CYP2D6 Structural Complexity with Long-Read Sequencing: Implications for Tamoxifen Precision Dosing in Thai Breast Cancer Patients.

Long-read (Oxford Nanopore) sequencing resolving structurally complex CYP2D6 alleles; activity score associated with endoxifen exposure

CYP2D6-mediated bioactivation of tamoxifen to endoxifen determines its efficacy, but the structurally complex alleles common in Asia complicate conventional genotyping. The authors apply Oxford Nanopore long-read sequencing to 492 Thai breast cancer patients (multivariable analysis in 361 on standard-dose tamoxifen). Long-read identifies 82 distinct diplotypes and resolves complex structural variation, including the non-identical CYP2D636+10 duplication. The CYP2D6 activity score is the strongest determinant of endoxifen exposure, with 46.55% of patients having decreased enzyme function.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A neat demonstration of long-read value for a pharmacogene notoriously hard to genotype, with a direct clinical consequence (tamoxifen dosing). It confirms that resolving CYP2D6 structural alleles is not just a technical exercise: it changes phenotype classification and hence the therapeutic decision.

Analysis by Dr Thibaut Benquey