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Updated: Jun 4, 2025
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
TP53 Mutation Is the Only Robust Mutational Biomarker for Outcome Found in a Consecutive Clinical Cohort of Real-Word
Marie Fredslund Breinholt1,2, Lone Schejbel1, Anne Ortved Gang2,3
1Department of Pathology, Herlev-Gentofte Hospital, Herlev, Denmark.
Introduction:
Large B-cell lymphoma (LBCL) taxonomy has moved in the direction of a molecular classification, but further clinical experience is needed. We present high-risk gene mutations, which predict outcome in an exploratory study of a consecutive real-world cohort of patients with primary LBCL treated with R-CHOP or R-CHOP-like therapy.
Methods:
The study was a Registry Study Research Project. Sixty-one patients with LBCL, who had a diagnostic tumor sample successfully examined with a 59-gene next-generation sequencing (NGS) panel as a part of routine clinical work, were included in an otherwise unselected cohort. Data were extracted from patient files and pathology reports.
Results:
Mutations in NOTCH2 (HR 9.69; 95% CI [2.46-38.11]; p = 0.0012), PRDM1 (HR 3.54; 95% CI [1.03-12.22]; p = 0.045), and TP53 (HR 5.89; 95% CI [1.71-20.32]; p = 0.005) were significantly associated with inferior survival in patients with primary LBCL treated with intention to cure with at least three series of R-CHOP or R-CHOP-like therapy. Neither MYD88 (HR 0.66; 95% CI (0.17-2.49), p = 0.54) nor CD79B (HR 0.84;95% CI (0.18-3.88), p = 0.82) mutations were associated with inferior survival.
Conclusion:
With a targeted gene panel and NGS methodology feasible in daily diagnostic routine, we identified high-risk gene mutations with a significant prognostic impact of which TP53 mutations were reproducible across validation cohorts.
