Genomic and transcriptomic characterization of atypical carcinoids of the lung

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 DESCRIPTION (provided by applicant): Lung neuroendocrine tumors (LNET) account for 30% of all lung cancer cases, and include well- differentiated typical and atypical carcinoids, and poorly differentiate and highly malignant small cell lung cancer (SCLC) and large cell neuroendocrine lung carcinoma (LCNEC). SCLC, which represents almost 70% of LNET, has so far no effective treatment, and a 5-year survival rate below 5%. Unlike other lung tumors (such as, adenocarcinomas), LNET do not seem to harbor promising therapeutic targets, warranting the need for further studies. Considering the fact that "trans-differentiation" from adenocarcinomas to SCLC can occur, and that different lung cancer subtypes can coexist, we hypothesize that a fraction of lung tumors might originate from each other. Similarities in clinica and pathological characteristics of atypical carcinoids and SCLC, together with preliminary genomic data on these tumors, suggest a possible "trans- differentiation" process from low aggressive AC to highly aggressive SCLC. If this holds true, since atypical carcinoids do not carry, in general, complex genomes, we would have a relatively simple system to identify the pathways or genes responsible for the development of the deadly SCLC. In this study we will apply to deep-sequencing strategies to characterize the genome and transcriptome of atypical carcinoids. Also, by comparing with available genomic data on the other LNET, we will try to identify any possible connection between low-grade and high-grade lung neuroendocrine tumors. Ultimately, we aim to shed light on the pathways responsible for the development of LNET to help identify early events that would allow detecting SCLC and LCNEC at stages in which surgical resection is still an option, as well as provide the patients with more promising therapeutic options.