e15174 Background: Endometrial cancer (EC) is the sixth most common malignancy among women worldwide, with over 420,000 new cases annually and a substantial disease burden in India. The 2013 TCGA classification introduced a molecular framework for EC; however, therapeutic advances such as immunotherapy have largely benefited the mismatch repair-deficient (MSI-H/dMMR) subset. Most patients have mismatch repair-proficient (pMMR) disease and continue to face limited treatment options in advanced or recurrent settings. Established biomarkers, including PD-L1, have shown limited predictive value. This study describes the genomic alterations identified in EC using a targeted next-generation sequencing (NGS) panel in a real-world cohort. Methods: This retrospective study included 112 patients with histologically confirmed endometrial carcinoma. Genomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) tumor samples with >20% tumor content. DNA was extracted using IVD manual isolation kits, and samples meeting predefined quality control criteria on the Agilent TapeStation 4200 were selected for library preparation. Sequencing was conducted using a custom 21-gene EC panel validated according to CAP and NABL standards on the MGI DNBSEQ-T7 platform. Somatic variants were annotated and interpreted following ACMG, AMP, and CAP guidelines. Results: Genomic alterations were identified in 73 of 112 cases (65.18%). Most patients presented with primary disease (92.86%), while 7.14% had metastatic disease, most commonly involving lymph nodes (37.5%) and omentum (25%). FIGO staging distribution was stage I (51.79%), stage II (36.61%), stage III (8.04%), and stage IV (3.57%). The most frequently altered genes were PTEN (21.05%), POLE (13.49%), and TP53 (12.83%), followed by ARID1A (8.22%), BRCA2 (5.92%), FGFR2 (4.93%), and BRCA1 (3.29%). Pathogenic alterations in mismatch repair genes were observed across MSH6 (4.28%), MSH2 (3.95%), MLH1 (3.29%), and PMS2 (1.97%). Additional lower-frequency alterations were identified in PIK3CA, POLG2, MUTYH, BRAF, CHEK2, and RET. Conclusions: This real-world genomic profiling study shows that targeted NGS identifies potentially actionable genomic alterations in a substantial proportion of patients with endometrial carcinoma. While mismatch repair gene alterations support immunotherapy use in a subset of cases, the predominance of alterations in pMMR tumors highlights the molecular heterogeneity of EC and the need for further exploration of biomarker-driven treatment strategies. These findings support the role of focused NGS panels in improving molecular characterization and informing personalized treatment considerations in endometrial carcinoma.
Dhabhar et al. (Thu,) studied this question.
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