TITLE:
Tumor Response to Temsirolimus for Epithelioid Angiomyolipoma and Novel Mutation of SMARCB1/INI1 Tumor Suppressor Gene
AUTHORS:
Jung Yong Hong, Jeeyun Lee, Kyoung-Mee Kim, Sung Joo Kim
KEYWORDS:
Epithelioid Angiomyolipoma, Temsirolimus, SMARCB1/INI1
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.13,
November
11,
2014
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 ofTSC1 (encodes harmartin) orTSC2 (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 inSMARCB1 (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.