Tumor Response to Temsirolimus for Epithelioid Angiomyolipoma and Novel Mutation of <i>SMARCB1/INI1</i> Tumor Suppressor Gene

Abstract

Epithelioid angiomyolipoma (EAML) is a rare morphologic variant of classic angiomyolipoma (AML), showing potentially malignant phenotype. AML is a benign mesenchymal tumor, which shows frequent inactivating mutations of TSC 1 (encodes harmartin) or TSC 2 (encodes tuberin) genes. Disruption of harmatin-tuberin complex and subsequent inappropriate activation of mTOR pathway is a distinct feature of AML. Thus, mTOR pathway inhibitors have shown significant clinical response in AML. Compared to the great success of mTOR inhibitors in AML, there is no standard therapy for EAML yet. Here, we present a patient with EAML who responded well to mTOR inhibitor (temsirolimus) but suffered rapid disease progression after cessation of temsirolimus. In addition, we performed Cancer Hotspot Panel (Ion AmpliSeq TM ) analysis to identify novel tumorigenic properties of EAML. Of note, Cancer Hotspot Panel analysis revealed novel missense mutation in SMARCB 1 (c.1119-41G > A) tumor suppressor gene and subsequent immunohistochemistry analysis also revealed weak and partial losses of SMARCB 1/ INI 1 protein in nuclei of tumor cells. In this study, we suggest that mTOR inhibitors also can be effective against EAML. However, the long-term efficacy of mTOR inhibitors in EAML needs to be supported in further studies. Furthermore, we speculate that the newly found missense mutation of SMARCB 1 /INI 1 gene can be the possible novel tumorigenic properties of EAML and highlights the possibility of further novel targeted therapy beyond mTOR inhibitors in EAML.