TP53 co-mutations in advanced lung adenocarcinoma: comparative bioinformatic analyses suggest ambivalent character on overall survival alongside KRAS , STK11 and KEAP1 mutations.

Autor:	Frille A; Department of Respiratory Medicine, Leipzig University, Leipzig, Germany., Boeschen M; Institute of Pathology, Leipzig University, Leipzig, Germany., Wirtz H; Department of Respiratory Medicine, Leipzig University, Leipzig, Germany., Stiller M; Institute of Pathology, Leipzig University, Leipzig, Germany., Bläker H; Institute of Pathology, Leipzig University, Leipzig, Germany., von Laffert M; Institute of Pathology, Leipzig University, Leipzig, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Apr 22; Vol. 14, pp. 1357583. Date of Electronic Publication: 2024 Apr 22 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1357583
Abstrakt:	Background: Recently, we could show that the co-mutations of KRAS + KEAP1 , STK11 + KEAP1 and KRAS + STK11 + KEAP1 lead to a significantly shorter median overall survival (mOS) across treatments by analyzing multiple datasets. TP53 , a tumor suppressor gene, plays a crucial role in regulating cell cycle progression. Its mutations occur in approximately 40-50% of non-small lung cancer (NSCLC). Co-occurrence of all four mentioned mutations has been a matter of debate for years. The aim of this study was to assess the distribution of these four mutations and the influence of the different co-mutational patterns on survival. Methods: We present a comparative bioinformatic analysis and refer to data of 4,109 patients with lung adenocarcinoma (LUAD). Results: Most of the mutations within the LUAD belong to TP53 -only (29.0%), quadruple-negative (25.9%) and KRAS -only (13.4%). Whereas TP53 -mutations seem to have protective effects in the context of further KEAP1 - and KRAS + KEAP1 - alterations (improved mOS), their role seems contrary if acquired in an already existing combination of mutations as KRAS + STK11 , KRAS + STK11 + KEAP1 and STK1 + KEAP1 . TP53 co-mutationshad a negative influence on KRAS -only mutated LUAD (mOS reduced significantly by more than 30%). Discussion: These data underline the need for complex mutational testing to estimate prognosis more accurately in patients with advanced LUAD. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This publication was funded by the Open Access Publishing Fund of Leipzig University, supported by the German Research Foundation (DFG). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. (Copyright © 2024 Frille, Boeschen, Wirtz, Stiller, Bläker and von Laffert.)
Databáze:	MEDLINE
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