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

Background: Recently, we could show that the co-mutations of + , + and + + lead to a significantly shorter median overall survival (mOS) across treatments by analyzing multiple datasets. , 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 -only (29.0%), quadruple-negative (25.9%) and -only (13.4%). Whereas seem to have protective effects in the context of further and + alterations (improved mOS), their role seems contrary if acquired in an already existing combination of mutations as + + + and + . co-mutationshad a negative influence on -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.