Observed ALK fusion/rearrangement frequency across comprehensive genomic profiling platforms in Japanese routine...

Clinically relevant ALK alterations are identified across routine comprehensive genomic profiling (CGP), but their observed frequency may vary according to testing context. Because ALK-directed treatment is primarily linked to fusion/rearrangement events, we sought to define a nationwide benchmark for interpreting ALK fusion/rearrangement findings across routine CGP settings in Japan.

We performed a retrospective descriptive analysis of anonymized aggregated Center for Cancer Genomics and Advanced Therapeutics data through March 31, 2025. Case-level observed frequencies within the CGP-tested cohort were evaluated across 97,343 cases, five CGP assays, 12 organ groups, and pooled tissue-based versus liquid-based settings. A supplementary fusion-only sensitivity analysis evaluated definitional dependence.

The overall case-level observed ALK fusion/rearrangement frequency within the CGP-tested cohort was 0.329% (320/97,343; 95% CI 0.294-0.367). Observed frequencies ranged from 0.152% for NCC Oncopanel to 0.598% for FoundationOne Liquid CDx (P < 0.001). When pooled by specimen context, observed frequency was 0.280% in tissue-based CGP and 0.561% in liquid-based CGP (P < 0.001). Thoracic tumors showed the highest observed frequency (1.988%), whereas liver tumors showed no positive cases. In the fusion-only sensitivity analysis, the overall frequency decreased to 0.234%, with a larger reduction in pooled liquid-based CGP than in pooled tissue-based CGP, reflecting reporting-category and context dependence rather than lower analytical sensitivity, while the broad directional pattern was preserved.

This nationwide C-CAT analysis provides an implementation-oriented CGP-cohort benchmark for panel-aware and specimen-context-aware interpretation of observed ALK findings; these case-level frequencies should not be interpreted as population prevalence.