Genomic and transcriptomic characterization of atypical carcinoids of the lung

肺部非典型类癌的基因组和转录组特征

• 批准号: 8881414
• 负责人: James Dowling MCKAY
• 金额: $ 5.65万
• 依托单位: INTERNATIONAL AGENCY FOR RES ON CANCER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8881414
• 关键词: Accounting; Adenocarcinoma; Carcinoid Tumor; Characteristics; Complex; Consensus; DNA Sequence Alteration; Data; Development; Disease; Early Diagnosis; Event; Evolution; Excision; Gene Expression Profile; Genes; Genome; Genomics; Human; Lesion; Light; Lung; Lung Neoplasms; Lung Neuroendocrine Neoplasm; Malignant - descriptor; Malignant Neoplasms; Malignant Small Cell; Malignant neoplasm of lung; Molecular; Mutate; Mutation; Neuroendocrine Cell; Neurosecretory Systems; Operative Surgical Procedures; Pathway interactions; Patients; Pattern; Process; Publishing; Relapse; Resected; Resistance; Smoking; Squamous Cell; Staging; Survival Rate; System; Therapeutic; Therapeutic Intervention; Transcript; chemotherapy; comparative; deep sequencing; effective therapy; exome sequencing; lung Carcinoma; lung small cell carcinoma; novel therapeutics; public health relevance; therapeutic target; transcriptome sequencing; transcriptomics; tumor

 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.

 描述（申请人提供）：肺神经内分泌肿瘤（LNET）占所有肺癌病例的30%，包括高分化的典型和非典型类癌，以及低分化和高度恶性的小细胞肺癌（SCLC）和大细胞神经内分泌癌肺癌（LCNEC）占 LNET 的近 70%，迄今为止尚无有效的治疗方法，且与其他癌症不同，其 5 年生存率低于 5%。对于肺部肿瘤（如腺癌），LNET 似乎没有有希望的治疗靶点，考虑到腺癌可能发生“转分化”，并且不同的肺癌亚型可以共存，因此需要进一步研究。 ，我们发现一小部分肺部肿瘤可能源自非典型类癌和 SCLC 的临床和病理特征的相似性，加上这些肿瘤的初步基因组数据，表明可能存在“反式”。从低侵袭性 AC 到高侵袭性 SCLC 的“分化”过程。如果这是真的，因为非典型类癌一般不携带复杂的基因组，我们将有一个相对简单的系统来识别导致致命性癌发展的途径或基因。在这项研究中，我们将应用深度测序策略来表征非典型类癌的基因组和转录组，此外，通过与其他 LNET 上的可用基因组数据进行比较，我们将尝试确定低级别和高级别之间的任何可能联系。级肺最终，我们的目标是阐明导致 LNET 发展的途径，以帮助识别早期事件，以便在手术切除仍然是一种选择的阶段检测 SCLC 和 LCNEC，并为患者提供更多信息。有希望的治疗选择。