2011
DOI: 10.1101/gad.2046711
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Abstract: Small cell lung cancer (SCLC) is an aggressive cancer often diagnosed after it has metastasized. Despite the need to better understand this disease, SCLC remains poorly characterized at the molecular and genomic levels. Using a genetically engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung, we identified several frequent, high-magnitude focal DNA copy number alterations in SCLC. We uncovered amplification of a novel, oncogenic transcription factor, Nuclear factor I/B (Nf… Show more

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Cited by 146 publications
(161 citation statements)
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References 35 publications
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“…To rigorously assess the activity of the combination of ABT-263 and AZD8055 in vivo, we used a GEMM of SCLC (36). Tumors are initiated in this model via conditional inactivation of both alleles of Tp53 and Rb1 in pulmonary neuroendocrine cells, resulting in the development of tumors that model the histology, metastatic spread, and acquired genetic alterations observed in human SCLC (37)(38)(39). Tumor-bearing SCLC GEMMs were randomized to receive no treatment, AZD8055 alone (16mg/ kg/qd), ABT-263 alone (80 mg/kg/qd), or both ABT-263 and AZD8055 and were treated for 21 d (Fig.…”
Section: Combination Of Abt-263 and Azd8055 Is Superior To Either Drugmentioning
confidence: 99%
“…To rigorously assess the activity of the combination of ABT-263 and AZD8055 in vivo, we used a GEMM of SCLC (36). Tumors are initiated in this model via conditional inactivation of both alleles of Tp53 and Rb1 in pulmonary neuroendocrine cells, resulting in the development of tumors that model the histology, metastatic spread, and acquired genetic alterations observed in human SCLC (37)(38)(39). Tumor-bearing SCLC GEMMs were randomized to receive no treatment, AZD8055 alone (16mg/ kg/qd), ABT-263 alone (80 mg/kg/qd), or both ABT-263 and AZD8055 and were treated for 21 d (Fig.…”
Section: Combination Of Abt-263 and Azd8055 Is Superior To Either Drugmentioning
confidence: 99%
“…Differently from noncancer cells, those altered gene programs in cancer cells have a striking dependence on continuous active transcription. For example, small cell lung cancer (SCLC) cells are addicted to lineage-specific and protooncogenic transcription factors that support their growth (2)(3)(4)(5)(6)(7). Similarly, triple-negative breast cancer (TNBC) is highly dependent on uninterrupted transcription of a specific key set of genes (8,9).…”
Section: Introductionmentioning
confidence: 99%
“…the mutation status seems not to be associated with age at diagnosis, clinical stage, the presence of certain histologic features, or overall survival, and such mutations are not found in normal tissues or tissues from other cancer types (2). Mutations are found in the KRAS gene-an EGFR signaling pathway gene-in 8 % of lung cancers but not in those that have an EGFR gene mutation (23). This shows that the pathogenesis of adenocarcinoma is different (16).…”
Section: Oncogenesmentioning
confidence: 99%
“…Dooley et al (23), using a new technique called wholegenome profiling, managed to pinpoint a gene that appears to drive progression of Sclc, from 15 % of lung cancer cases. The authors found extra copies of a few short stretches of DNA, including a segment of chromosome 4 that includes the nuclear Factor i/B (NFIB) gene.…”
Section: New Candidate Genes Associated With Lung Cancermentioning
confidence: 99%