Project description:Lung cancer is the leading cause of cancer death in USA. Squamous Cell Carcinoma (SCC) is one of the subtypes of lung cancer. It is still largely unknown which genes or pathways regulate lung SCC development. Recently, we found JNK1/2 pathway was inhibited in mouse lung SCC induced by double ablation of Pten and Lkb1 in mouse lung epithelial cells. Now we aim to identify a genome-wide molecular signature of JNK1/2 signaling in mouse squamous cell carcinoma cells and determine pathways that transduce JNK1/2 signaling.
Project description:Lung cancer, majorly divided into non-small cell lung cancer (80-85%) and small cell lung cancer (15-20%), is the leading cause of cancer death in USA. Squamous Cell Carcinoma (SCC) is one of major subtypes of non-small cell lung cancer. Although genomic analysis of tumors from SSC patients have identified frequently mutated genes in these tumors, it’s still largely unknown which genes determine SCC development. Now we found that ablation of alone Lkb1 could induce SCC around 12 months of age. Therefore, transcriptome analysis of lung SCC of CCSPiCreLkb1f/f mice will help us understand how Lkb1 regulates the development of lung SCC.
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. These aberrations are indeed among the most frequent aberrations in lung SCC and correlate with SCC patient's poor prognosis. We precisely map regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC. We moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. Keywords: ArrayCGH, Lung Squamous Cell Carcinoma, 3q26.3, SOX2
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. These aberrations are indeed among the most frequent aberrations in lung SCC and correlate with SCC patient's poor prognosis. We precisely map regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC. We moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. Keywords: ArrayCGH, Lung Squamous Cell Carcinoma, 3q26.3, SOX2 Profiling of 26 advanced (stage III) lung SCC. Replicates : each tumor sample is hybridized together with a normal dna sample to one microarray. Each microarray contain 3 replicates per BAC clone.
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. Chromosome 3 aberrations are indeed among the most frequent alterations in lung SCC and correlate with SCC patient's poor prognosis. We have precisely mapped regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC (GSE14859) amd moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. These amplicons were precisely mapped in these tumors using arraCGH with a 3q26.3 dedicated tiling array. Keywords : ArrayCGH, lung Squamous Cell Carcinoma, 3q26.3, SOX2 Keywords: ArrayCGH
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. Chromosome 3 aberrations are indeed among the most frequent alterations in lung SCC and correlate with SCC patient's poor prognosis. We have precisely mapped regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC (GSE14859) amd moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. These amplicons were precisely mapped in these tumors using arraCGH with a 3q26.3 dedicated tiling array. Keywords : ArrayCGH, lung Squamous Cell Carcinoma, 3q26.3, SOX2 Keywords: ArrayCGH Profiling of 5 advanced (stage III) lung SCC using a chromosome 3 array providing 3q26.3-q27 tiling coverage. Replicates : each array contains three replicates per clone and each sample is hybridized to two arrays, results are subsequently averaged.
Project description:Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. We recently identified the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC, and demonstrated that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Reduced levels of GRHL3 and its target gene PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data defines the miR-21-GRHL3-PTEN-axis as a critical tumor suppressor pathway in SCC.
Project description:Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. We recently identified the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC, and demonstrated that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Reduced levels of GRHL3 and its target gene PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data defines the miR-21-GRHL3-PTEN-axis as a critical tumor suppressor pathway in SCC. Total RNA was isolated from two SCC primary tissue samples and their matched normal skin controls.
Project description:To identify gene expression biomarkers associate with asbestos-related lung squamous cell carcinoma, we analyzed gene expression profiles for a total of 56 lung squamous cell carcinomas using 44K Illumina Gene Expression microarrays. Twenty-six cases had lung asbestos body counts above levels associated with urban dwelling (ARLC-SCC: asbestos-related lung cancer-squamous cell carcinoma) and 30 cases had no lung asbestos bodies (NARLC-SCC: non-asbestos related lung cancer- squamous cell carcinoma). Genes differentially expressed between ARLC-SCC and NARLC-SCC were identified on fold change and P-value, and then prioritised using gene ontology.