Abstract 297P
Background
Renal angiomyolipoma (AML) encompasses benign tumors with histological variants like Lipomatous AML (L-AML) and myomatous AML (M-AML), whereas epithelioid AML (eAML) represents a potentially malignant subtype. Further genomic studies are necessary for elucidating its pathogenesis and clinical implications.
Methods
Thirty-five tumor and blood samples were examined for somatic mutation by performing whole-exome sequencing (WES). In addition, a total of 71 formalin-fixed paraffin-embedded (FFPE) slices and clinicopathological data of eAML patients were enrolled as a validation cohort. The oncodriveCLUST was used to screen the driver genes (DGs) and MutSigCV was utilized to identify significantly mutated genes with default parameters.
Results
TSC2 is the most frequently mutated pathogenic gene known to be associated with AML, with a mutation frequency of 69%. Across three subtypes of AML, TSC2, POLDIP2, NEFH, and MUC2 were identified as potential DGs, while RHPN2, ASXL1, TOP3B, and USP35 were identified as differential mutation genes. In addition, we observed significant cytobands between three types, including deletions of 3p26.3, 5p13.1, 6p22.1, and 11p11.11. Clonal evolution analysis revealed that L-AML and eAML or M-AML and eAML from the same patient may originated from a most recent common ancestor, retaining these early mutations before clonal expansion and acquiring additional mutations after divergence. In the validation cohort, TSC2 and POLDIP2 revealed significantly higher expression in tumor tissues compared to normal tissues, while NEFH and MUC2 were found to be significantly more highly expressed in normal tissues than in tumor tissues. Survival analysis indicated that low expression of TSC2 and POLDIP2, as well as high expression of NEFH and MUC2 were significantly correlated with a favorable overall survival (OS) for eAML patients. Compared with the high expression group, TSC2 and POLDIP2 low expression group achieved better objective response rates for Everolimus targeted therapy.
Conclusions
This study provides a comprehensive overview of the genomic landscape and clinical features of renal eAML and benign AML, highlighting the heterogeneity and complexity of the renal AML subtypes.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Fudan University Fuqing scholars Project (no. FQXZ202304A).
Disclosure
All authors have declared no conflicts of interest.