Dataset Information

Lung normal control - samples

ABSTRACT: SCLC matched normal genotypes

PROVIDER: EGAD00010000278 | EGA |

REPOSITORIES: EGA

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Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.

Rudin Charles M CM Durinck Steffen S Stawiski Eric W EW Poirier John T JT Modrusan Zora Z Shames David S DS Bergbower Emily A EA Guan Yinghui Y Shin James J Guillory Joseph J Rivers Celina Sanchez CS Foo Catherine K CK Bhatt Deepali D Stinson Jeremy J Gnad Florian F Haverty Peter M PM Gentleman Robert R Chaudhuri Subhra S Janakiraman Vasantharajan V Jaiswal Bijay S BS Parikh Chaitali C Yuan Wenlin W Zhang Zemin Z Koeppen Hartmut H Wu Thomas D TD Stern Howard M HM Yauch Robert L RL Huffman Kenneth E KE Paskulin Diego D DD Illei Peter B PB Varella-Garcia Marileila M Gazdar Adi F AF de Sauvage Frederic J FJ Bourgon Richard R Minna John D JD Brock Malcolm V MV Seshagiri Somasekar S

Nature genetics 20120902 10

Small-cell lung cancer (SCLC) is an exceptionally aggressive disease with poor prognosis. Here, we obtained exome, transcriptome and copy-number alteration data from approximately 53 samples consisting of 36 primary human SCLC and normal tissue pairs and 17 matched SCLC and lymphoblastoid cell lines. We also obtained data for 4 primary tumors and 23 SCLC cell lines. We identified 22 significantly mutated genes in SCLC, including genes encoding kinases, G protein-coupled receptors and chromatin-m ...[more]

PMID: 22941189

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Project description:Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis due to early dissemination and rapid growth. We here analyze gene expression profile of 23 clinical SCLC samples. EZH2 was found to be highly expressed in SCLC samples compared to 42 normal tissues including the normal lung, and other PRC2 members, SUZ12 and EED, were also highly expressed in SCLC. To obtain target genes of PRC2 in SCLC, H3K27me3 mark was mapped in three SCLC cell lines, Lu130, H209 and DMS53, and compared to normal small airway epithelial cells (SAEC). Whereas H3K27me3(+) genes in SAEC were significantly overlapped with PRC-target genes in ES cells (P=1.7x10-31), genes with H3K27me3 in SCLC cell lines but not in SAEC were not significantly overlapped with PRC-target genes in ES cells (P=0.64). These genes with H3K27me3 specifically in SCLC cell lines but not in SAEC showed decreased expression, not only in SCLC cell lines but also in clinical SCLCs, and showed enrichment of GO-terms such as plasma membrane (P=8.1x10-21) and cell adhesion (P=1.7x10-8). Introduction of JUB, a gene showing specific H3K27me3 modification and the strongest repression in the three SCLC cell lines, resulted in repression of cellular growth in DMS53. In clinical SCLC cases, lower JUB level correlated to shorter survival (P=0.002), or a set of PRC target genes (JUB, EPHB4) and marker genes of classic type SCLC (GRP, ASCL1) correlated to shorter survival (P=0.0001) and classified SCLC into two groups with distinct prognosis. Growth of SCLC cell lines was repressed when treated with 3-Deazaneplanocin A, an inhibitor against PRC2. It is suggested that high expression of PRC2 in SCLC contributed to repression of genes including non-PRC-target genes in ES cells, and that the gene repression may play a role in genesis of SCLC. Gene expression in 23 clinical SCLC samples, 42 normal tissue samples, 3 small cell lung cancer (SCLC) cell lines, and normal small airway epithelial cell (SAEC) was analyzed by Affymetrix arrays. This dataset is part of the TransQST collection.

Dataset Information

Lung normal control - samples

Publications

Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.

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