Jung Yong Hong¹, Jeeyun Lee^2*, Kyoung-Mee Kim³, Sung Joo Kim^4*

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¹ Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea.
² Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
³ Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
⁴ Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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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 TSC1 (encodes harmartin) or TSC2 (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 AmpliSeqTM) analysis to identify novel tumorigenic properties of EAML. Of note, Cancer Hotspot Panel analysis revealed novel missense mutation in SMARCB1 (c.1119-41G > A) tumor suppressor gene and subsequent immunohistochemistry analysis also revealed weak and partial losses ofSMARCB1/INI1 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 ofSMARCB1/INI1 gene can be the possible novel tumorigenic properties of EAML and highlights the possibility of further novel targeted therapy beyond mTOR inhibitors in EAML.

Keywords: Epithelioid Angiomyolipoma, Temsirolimus, SMARCB1/INI1

Cite this paper: Hong, J. , Lee, J. , Kim, K. and Kim, S. (2014) Tumor Response to Temsirolimus for Epithelioid Angiomyolipoma and Novel Mutation of SMARCB1/INI1 Tumor Suppressor Gene. Journal of Cancer Therapy, 5, 1215-1222. doi: 10.4236/jct.2014.513123.

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