Study

Comprehensive genomic profiles of small cell lung cancer

Study ID Alternative Stable ID Type
EGAS00001000925 Other

Study Description

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. We found bi-allelic inactivation of TP53 and RB1 in nearly all the tumors analyzed, sometimes by complex genomic rearrangements. Two tumors with wild-type RB1 had evidence of chromothripsis leading to overexpression of Cyclin D1, revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumor suppressors TP53 and RB1 is obligatory in SCLC. We further discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In few cases, SCLC tumors exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signaling in a pre-clinical SCLC mouse model dramatically reduced the number of tumors and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic ... (Show More)

Study Datasets 3 datasets.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001244
RNA-sequencing (RNA-seq) was performed with RNA extracted from fresh-frozen human tumor tissue samples. cDNA libraries were prepared from poly-A selected RNA applying the Illumina TruSeq protocol for mRNA. The libraries were then sequenced with a 2 x 100bp paired-end protocol to a minimum mean coverage of 30x of the annotated transcriptome.
Illumina HiSeq 2000 59
EGAD00001001273
Whole genome sequencing was performed with DNA extracted from fresh-frozen tumor and normal material. Short insert DNA libraries were prepared with the TruSeq DNA PCRfree sample preparation kit (Illumina) for paired-end sequencing at a minimum read length of 2x100bp. Human DNA libraries were sequenced to an average coverage of minimum 30x for both tumor and matched normal. Murine DNA libraries of tumor and matched normal were both sequenced to a coverage of 25x.
Illumina HiSeq 2000 100
EGAD00010000558
SNP 6.0 arrays of small cell lung cancer
Affymetrix SNP 6.0 54

Who archives the data?

Publications

Citations

Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...
Retrieving...