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PubMed · 42018651

High tumor mutational burden and PIK3CA mutations correlate with poor Merkel cell carcinoma-specific survival.

Matheus Lobo·Furkan Bahar·Julia L Schnabel·Joao P Duprat Neto·Aniket Shetty·Karam Khaddour·Manisha Thakuria·Ann W Silk·James A DeCaprio
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Abstract

Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma of the skin characterized by poor prognosis. This study aimed to explore the relationship between genetic alterations, tumor mutational burden (TMB), and MCC-specific survival (MCC-SS) in patients who underwent genomic profiling of tumors with OncoPanel. Univariate and multivariable analysis were used to assess the impact of genetic alterations on MCC-SS. Of the 188 identified patients, 164 were included in the analysis. The cohort had a mean age of 72.4 years (SD = 11.03), including 61.6% male. The median TMB was 5.32 (IQR = 3.04-25.53). Kaplan-Meier curves by high versus low TMB were significantly different (log-rank test, P = 0.017). PIK3CA (adjusted P = 0.003), SETBP1 (adjusted P = 0.002), KDR (adjusted P = 0.028), and RET (adjusted P = 0.033) were selected for multivariable analysis. In the multivariable regressions, only PIK3CA (HR = 2.07 [95% CI, 1.10-3.88]; P = 0.024) remained significant. PIK3CA remained significant across prespecified sensitivity analyses. In this study, high TMB and PIK3CA alterations were associated with poor MCC-SS. Identifying a higher-risk subgroup may inform risk stratification and motivate further evaluation of PI3K pathway targeting in future studies.

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HumansClass I Phosphatidylinositol 3-KinasesMaleCarcinoma, Merkel CellFemaleAgedMutationSkin NeoplasmsAged, 80 and overPrognosisMiddle AgedKaplan-Meier EstimateBiomarkers, TumorDermatologyMolecular pathologyOncogenesOncologySkin cancerVirologyJournal ArticleResearch Support, N.I.H., Extramural

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Matheus Lobo, Furkan Bahar, Julia L Schnabel, Joao P Duprat Neto, Aniket Shetty, Karam Khaddour, Manisha Thakuria, Ann W Silk, James A DeCaprio. 2026-04-22. High tumor mutational burden and PIK3CA mutations correlate with poor Merkel cell carcinoma-specific survival.. https://doi.org/10.1172/jci.insight.197108

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