Project description:Here we describe novel murine models of pulmonary adenocarcinoma (ADC) and sarcomatoid carcinoma (PSC) driven by the loss of two tumor suppressors: deletion of Trp53 and Pten. Combined deletion of Pten and Trp53 in the lungs of adult conditional mice leads to the development of both ADC and PSC irrespective of the lung targeted cell type or naphthalene induced airway epithelial regeneration. Although this model shows long latency periods and incomplete penetrance for tumor development, it is the first PSC mouse model reported so far, and sheds light on the relationships between ADC and PSC and their cells of origin. Moreover, human ADC show strong transcriptomic similarities to mouse PSC, providing a link between these tumor types and human ADC. Ablation of Trp53 and Pten in pulmonary cells was achieved by intratracheal administration of purified Ad5-CMVcre or Ad5-K5cre (Du Page et al, 2009) to Trp53F/F; PtenF/F 8–10 week old mice. Mice were sacrificed at different time points after the Ad5-cre infection and tumors processed for whole transcriptome analysis. As control animals, Trp53F/F; PtenF/F littermates were used.
Project description:Pulmonary sarcomatoid carcinomas (PSCs) are rare and aggressive histological types of non-small cell lung cancer (NSCLC) with a median overall survival of about 9-12 months. In detail, PSCs comprise five different histological subtypes: pleomorphic carcinoma (PLC), giant cell carcinoma (GCC), spindle cell carcinoma (SCC), carcinosarcoma (CS) and pulmonary blastoma (PB). Preoperative pathological diagnosis may fail to identify these tumors and therapeutic options are still limited. PSCs have been scarcely characterized from a molecular point of view because of their rarity, and to date no specific markers have been found for PSCs in comparison with other NSCLC types. In this study a highly sensitive amplicon based whole transcriptome quantification analysis was performed, using the Ion AmpliSeq Transcriptome Human Gene Expression Kit (Life Technologies) on a selected series of 14 PSCs (1 PB, 4 CS, 2 SCC, 2 GCC, 5 PLC) and 3 samples of normal lung parenchyma. PSCs expression data were then compared with transcriptome data of lung adenocarcinoma and squamous cell carcinoma available on The Cancer Genome Atlas database. Thirty-eight genes specifically deregulated in PSC samples were identified. Among these, IGJ and SLMAP were validated by immunohistochemistry on an independent cohort (30 PSCs, 31 lung adenocarcinoma and 31 squamous cell carcinoma cases). Furthermore, a pathway enrichment analysis, performed on differentially expressed genes, revealed that FOXO signalling and Fanconi Anemia pathways, playing a pivotal role in cancer development and progression, are enriched in PSC tumors. The description of peculiar molecular profiles besides increasing our knowledge on PSCs biology may suggest new diagnostic and therapeutic strategies.
Project description:The study involves whole exome sequencing of 20 primary tumors obtained from lung squamous carcinoma patients of Indian origin. With this, we aim to describe the mutational profile of this specific subset of lung cancer patients. This knowledge will further allow us to gain an insight into potentially actionable genomic alterations prevalent in Indian lung squamous carcinoma.
Project description:DNA methylation data for Pulmonary Sarcomatoid Carcinoma (PSC) patients were generated using the Infinium MethylationEPIC Kit (Illumina, cat. no. WG-317-1001) or HumanMethylation450 BeadChip Kit (Illumina, cat. no. WG-314-1003).
Project description:DNA methylation data for Pulmonary Sarcomatoid Carcinoma (PSC) patients were generated using the Infinium MethylationEPIC Kit (Illumina, cat. no. WG-317-1001) or HumanMethylation450 BeadChip Kit (Illumina, cat. no. WG-314-1003).
