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| Status |
Public on Apr 22, 2010 |
| Title |
Array CGH-based Characterization of Genetic Alterations in Pulmonary Neuroendocrine Tumors |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on Array Comparative Genomic Hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal (GI) carcinoids. In contrast to the relatively stable karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. Recurrent CN alterations of a total of 203 genes, including the RB1 gene, and 59 microRNAs, most of which locate in the DLK1-DIO3 domain, were observed in SCLC tumors, bronchial carcinoids and carcinoids of GI origin; in contrast, CN alterations of the TP53 gene and the MYC family members were observed more frequently in SCLC. These findings suggest the existence of partially shared tumor-specific CN alterations in these tumors. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resemble that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.
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| Overall design |
Carcinoids, including 19 bronchial carcinoids and 9 carcinoid of gastrointestinal origin, and small cell lung cancer, including 33 patients' tumor samples and 13 cell line samples, were compared.
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| Contributor(s) |
Voortman J, Lee J, Killian JK, Suuriniemi MM, Wang Y, Lucchi M, Smith WI Jr, Meltzer P, Wang Y, Giaccone G |
| Citation(s) |
20615970 |
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| Submission date |
Apr 22, 2010 |
| Last update date |
Dec 06, 2012 |
| Contact name |
Jih-Hsiang Lee |
| E-mail(s) |
leej15@mail.nih.gov
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| Organization name |
National Cancer Institute
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| Department |
Medical oncology branch
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| Street address |
9000 Rockville Pike, building 10 8N254
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20852 |
| Country |
USA |
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| Platforms (2) |
| GPL4093 |
Agilent-014698 Human Genome CGH Microarray 105A (G4412A) |
| GPL10123 |
Agilent-022060 SurePrint G3 Human CGH Microarray 4x180K (Feature Number version) |
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| Samples (74)
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| Relations |
| BioProject |
PRJNA125819 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE21468_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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