This correspondence comments on the genetic landscape study by Lindner et al., which identified CBL deletion at 11q23.1-3 as a potential prognostic biomarker in stage II melanoma. The original analysis was performed on a cohort of 193 therapy‑naïve patients. The correspondence authors note the strength of using a relatively large, untreated cohort for prognostic biomarker discovery and value the multivariate approach applied in the primary study.
Lindner et al. report that deletion of the 11q23.1-3 region, encompassing CBL, was associated with prognosis in the overall stage II melanoma cohort. The correspondence recognises this result as a compelling starting point for further biomarker development and translational work. The authors emphasise that the cohort‑level multivariate analysis supporting this association provides a reasonable foundation for hypothesis generation about CBL as a driver gene and prognostic marker.
The correspondence draws attention to subgroup findings reported for molecular subtypes (including BRAF, RAS, NF1, and Triple‑WT). Specifically, in the RAS‑mutated subgroup the original paper reported an unadjusted p = 0.044 for relapse‑free survival. The correspondence authors point out that when more rigorous adjustment was applied, the adjusted p (Padj) was 0.178, indicating the subgroup result may not reach strict statistical significance. They caution that unadjusted p‑values in exploratory subgroup analyses can be misleading if presented without clear context or appropriate correction for multiple comparisons.
To reduce the risk of Type I errors in exploratory subgroup work, the correspondence recommends adjusting for multiple testing when examining prognostic associations across several genomic subtypes. The authors cite standard guidance on subgroup reporting in clinical research and recommend aligning biomarker reporting with established best practice frameworks such as the REMARK reporting recommendations for tumour marker prognostic studies. Emphasising adjusted metrics and standardised presentation helps readers assess the robustness of subgroup associations and supports reproducibility.
The authors highlight that translating cohort‑level prognostic associations into specific subgroup stratifications requires attention to possible confounding factors, including sub‑stage within stage II disease. They suggest that sub‑stage distribution and other clinical covariates could influence subgroup outcomes and should be considered when interpreting molecular subtype interactions with the CBL deletion. The correspondence encourages careful contextualisation of subgroup inferences rather than over‑interpretation of marginal or unadjusted results.
In summary, the correspondence commends Lindner et al. for identifying 11q23.1-3 (CBL) deletion as a candidate prognostic marker in stage II melanoma and for using a robust multivariate analysis in a therapy‑naïve cohort of 193 patients. However, the authors advise caution when interpreting subgroup signals — particularly where unadjusted p‑values are reported — and recommend routine use of multiple testing adjustment and adherence to reporting standards such as REMARK. They also note that sub‑stage confounding should be considered during subgroup stratification.
Author and publication details provided in the correspondence: Jingyi Han and Xinger Gao contributed equally (formal analysis and original draft); Wenjun Jiang contributed conceptualisation and editing. All authors are affiliated with the Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University. The correspondence was published in British Journal of Cancer on 21 September 2026 and the authors declared no competing interests.
References and related materials cited in the correspondence include the Lindner et al. stage II melanoma genetic landscape study, guidance on subgroup reporting in clinical research, the Cancer Genome Atlas melanoma classification, AJCC staging updates, and the REMARK reporting recommendations. The correspondence focuses on methodological clarity and appropriate statistical interpretation rather than providing new experimental data or clinical recommendations.