SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures

被引：111

作者：

Tlemsani, Camille ^{[1
,6
]}

Pongor, Lorinc ^{[1
]}

Elloumi, Fathi ^{[1
]}

Girard, Luc ^{[4
]}

Huffman, Kenneth E. ^{[4
]}

Roper, Nitin ^{[1
]}

Varma, Sudhir ^{[1
]}

Luna, Augustin ^{[5
]}

Rajapakse, Vinodh N. ^{[1
]}

Sebastian, Robin ^{[1
]}

Kohn, Kurt W. ^{[1
]}

Krushkal, Julia ^{[2
]}

Aladjem, Mirit, I ^{[1
]}

Teicher, Beverly A. ^{[2
]}

Meltzer, Paul S. ^{[3
]}

Reinhold, William C. ^{[1
]}

Minna, John D. ^{[4
]}

Thomas, Anish ^{[1
]}

Pommier, Yves ^{[1
]}

机构：

[1] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] NCI, Biometr Res Program, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA

[3] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[4] UT Southwestern Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA

[5] Dana Farber Canc Inst, cBio Ctr, Dept Data Sci, Div Biostat, Boston, MA 02115 USA

[6] Paris Descartes Univ, Cochin Inst, INSERM U1016, F-75014 Paris, France

来源：

CELL REPORTS | 2020年 / 33卷 / 03期

关键词：

DNA METHYLATION; MYC; EXPRESSION; GENE; AMPLIFICATION; PACKAGE; INTEGRATION; TRANSCRIPT; LANDSCAPE; EVOLUTION;

D O I：

10.1016/j.celrep.2020.108296

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

CellMiner-SCLC (https://discover.nci.nih.gov/ScicCellMinerCDB/) integrates drug sensitivity and genomic data, including high-resolution methylome and transcriptome from 118 patient-derived small cell lung cancer (SCLC) cell lines, providing a resource for research into this "recalcitrant cancer." We demonstrate the reproducibility and stability of data from multiple sources and validate the SCLC consensus nomenclature on the basis of expression of master transcription factors NEUROD1, ASCU , POU2F3, and YAP1 Our analyses reveal transcription networks linking SCLC subtypes with MYC and its paralogs and the NOTCH and HIPPO pathways. SCLC subsets express specific surface markers, providing potential opportunities for antibody-based targeted therapies. YAP1-driven SCLCs are notable for differential expression of the NOTCH pathway, epithelial-mesenchymal transition (EMT), and antigen-presenting machinery (APM) genes and sensitivity to mTOR and AKT inhibitors. These analyses provide insights into SCLC biology and a framework for future investigations into subtype-specific SCLC vulnerabilities.

引用

页数：20

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