Abstract PO-010: Kidney angiomyolipomas are defined by a unique transcriptomic profile and H3K27ac chromatin state

Background: Kidney angiomyolipomas (AML) are benign mesenchymal tumors that are commonly seen in Tuberous Sclerosis Complex (TSC), a rare genetic neurocutaneous disorder, but also occur sporadically. Kidney AML are due to either TSC1 or TSC2 biallelic loss, whereas other somatic genetic events are rare and do not contribute to tumor development. We hypothesized that the chromatin state and master transcription factors are also drivers of kidney angiomyolipoma growth, alongside mTORC1 hyperactivation. Material and Methods: We performed whole transcriptome RNA-sequencing on 28 kidney AML, and ChIP-seq for H3K27ac (a histone modification that marks open chromatin and regulates high transcription of nearby genes) on 25 kidney AML, a human kidney AML derived TSC2 null cell line (621-101), and a pigmented melanoma cell line (SK-MEL30). ChIP-Seq for MITF (Microphthalmia-associated transcription factor) was also carried out on three kidney AML tumors and SK-MEL30 cells. Functional studies were performed to assess the oncogenic role of MITF in vitro and in vivo. Results: Differential expression analyses of kidney AML compared to both The Cancer Genome Atlas (TCGA) tumors and GTEx normal tissues revealed 347 differentially expressed genes (DEGs), including 18 transcription factors (TFs; FDR/adjusted p-value =3 sections per tumor) compared to adjacent normal tissue. Knock out of MITF-A by CRISPR/Cas9 showed reduction in cell growth (82%, p Citation Format: Krinio Giannikou, Clemens K. Probst, Mahsa Zarei, Xintao Qiu, Melissa Duarte, Nikolas Kesten, Zachary Hebert, Raga Vadhi, Alba Font-Tello, Paloma Cejas, Charles H. Yoon, Chin-Lee Wu, Myles Brown, Elizabeth P. Henske, Henry Long, David J. Kwiatkowski. Kidney angiomyolipomas are defined by a unique transcriptomic profile and H3K27ac chromatin state [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-010.