<i>TTN</i> Mutation in Endometrial Endometrioid Carcinoma Is Associated with Poor Clinical Outcomes and High Tumor Mutation Burden

Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the <i>TTN</i> mutant group showed shorter progression-free survival (<i>p</i> &lt; 0.001) and overall survival (<i>p</i> &lt; 0.001) than <i>TTN</i> wild-type group. Additionally, we discovered that the number of <i>TTN</i> mutations per sample was significantly linked with TMB-WES in CHCAMS cohort and TCGA cohort (<i>p</i> &lt; 0.05). And the number of <i>TTN</i> mutations per sample in <i>POLE</i> mutant group was greater than in the <i>POLE</i> wild-type group (<i>p</i> &lt; 0.0001). In conclusion, <i>TTN</i> mutation may serve as a biomarker for EEC prognosis. <i>TTN</i> mutation is also associated with WES-TMB, and could be a simplified TMB measurement technique.