LYN mutations in breast cancer: hypothesis-generating evidence for an association with central nervous system metastasis and domain-level insights

Across pooled cohorts, LYN mutation is associated with increased odds of CNS metastasis, and domain context appears informative, with a small-sample, FDR-borderline enrichment at the SH4/Unique N-terminus. The truncating-class signal is exploratory given limited power. Signals by domain (notably SH4/Unique) are exploratory and require independent validation in larger, uniformly annotated datasets. Given small mutant denominators and ever-CNS endpoint capture, findings are hypothesis-generating and not actionable for risk stratification or treatment selection. Results motivate domain-aware annotation in future validation studies and mechanistic work.