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Figure 8 from A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma Cell Lines, PDX, and Patient Samples

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posted on 2024-10-30, 15:00 authored by Yasuhiro Arakawa, Fathi Elloumi, Sudhir Varma, Prashant Khandagale, Ukhyun Jo, Suresh Kumar, Nitin Roper, William C. Reinhold, Robert W. Robey, Naoko Takebe, Michael M. Gottesman, Craig J. Thomas, Valentina Boeva, Alfredo Berruti, Andrea Abate, Mariangela Tamburello, Sandra Sigala, Constanze Hantel, Isabel Weigand, Margaret E. Wierman, Katja Kiseljak-Vassiliades, Jaydira Del Rivero, Yves Pommier

The CU-ACC1 cell line is sensitive to temozolomide as it lacks MGMT and is MMR proficient, whereas CU-ACC2 cells are resistant to temozolomide because of MMR deficiency. A, CU-ACC1 and CU-ACC2 do not express MGMT transcripts. Univariate scatterplot of MGMT transcriptional expression levels vs. MGMT gene promoter methylation levels in the ACC cell line dataset. B, MGMT protein expression levels in CU-ACC1, CU-ACC2, NCI-H295R, and SW-13. Proteins were extracted from each cell line, and MGMT expression was assessed by Western blotting. C, The CU-ACC2 cell line is defective in MMR due to lack of expression of the MSH2 gene. Univariate scatter plot of MHS2 transcript levels vs. MSH2 gene copy number in the ACC cell lines data set. D, Dose–response curves of temozolomide in CU-ACC1, CU-ACC2, NCI-H295R, and SW-13. Cell viability was assessed after 72 hours under the indicated drug concentrations by CellTiter-Glo assay.

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ARTICLE ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and highly heterogeneous disease with a notably poor prognosis due to significant challenges in diagnosis and treatment. Emphasizing on the importance of precision medicine, there is an increasing need for comprehensive genomic resources alongside well-developed experimental models to devise personalized therapeutic strategies. We present ACC_CellMinerCDB, a substantive genomic and drug sensitivity database (available at https://discover.nci.nih.gov/acc_cellminercdb) comprising ACC cell lines, patient-derived xenografts, surgical samples, and responses to more than 2,400 drugs examined by the NCI and National Center for Advancing Translational Sciences. This database exposes shared genomic pathways among ACC cell lines and surgical samples, thus authenticating the cell lines as research models. It also allows exploration of pertinent treatment markers such as MDR-1, SOAT1, MGMT, MMR, and SLFN11 and introduces the potential to repurpose agents like temozolomide for ACC therapy. ACC_CellMinerCDB provides the foundation for exploring larger preclinical ACC models. ACC_CellMinerCDB, a comprehensive database of cell lines, patient-derived xenografts, surgical samples, and drug responses, reveals shared genomic pathways and treatment-relevant markers in ACC. This resource offers insights into potential therapeutic targets and the opportunity to repurpose existing drugs for ACC therapy.

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