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Transcriptomic analyses of high-grade neuroendocrine carcinoma of gynecologic origin

ABSTRACT: Transcriptomic analyses of high-grade neuroendocrine carcinoma of gynecologic origin

PROVIDER: PRJNA662104 | ENA |

REPOSITORIES: ENA

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Transcriptomic analyses of high-grade neuroendocrine carcinoma of gynecologic origin

Project description:High-grade neuroendocrine carcinomas (NECs) of the cervix are rare, aggressive cancers accounting for about 1-1.5% of all cervical cancer. The 5-year survival is up to 36% for early-stage disease; however, the advanced-stage disease has <10% survival, with relapse rates exceeding 90%. These cancers are likely to have a vascular invasion and nodal or visceral metastasis. Unfortunately, NEC of the cervix affects young women with a median age of 37. High-grade NECs of other gynecologic origins are even rarer, share similar aggressive behavior and poor outcomes. We performed stranded paired-end RNA-seq of 13 samples, including 12 samples with matched whole exome sequencing (WES) data. Sites of origin for tumors in our cohort were the cervix (69%), ovary (19%), and endometrium (12%). The median number of prior lines of therapy was 1. Median PFS and OS were 1 and 12 months, respectively, indicating their highly lethal nature. Comparing transcriptomic profiles with TCGA cervical and ovarian cancers, chromatin assembly and nucleosome organization were the top GO functions for significantly over-expressed genes in our cohort. Remarkably, under-expressed genes in our cohort were enriched for protein modification and catabolic processes, and neutrophil-mediated immunity. Compared to small cell lung cancer (SCLC), our cohort showed highly distinct transcriptomic patterns, and represented the YAP1 high molecular subtype.

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Comprehensive Sequencing of High Grade Neuroendocrine Neoplasms

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ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers

Project description:ChIP-Seq analysis performed on 5 ASCL1(+) cell lines and 2 ASCL1 (-) cell lines in order to understand the transcriptome of ASCL1 as it pertains to high-grade neuroendocrine lung cancers 5 ASCL1(+) lung cancer cell lines and 2 ASCL1(-) lung cancer cell lines were compared using ChIP-Seq analysis

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Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

Project description:This phase I trial studies the side effects and best dose of cixutumumab when given together with everolimus and octreotide acetate in treating patients with advanced low- or intermediate-grade neuroendocrine cancer. Monoclonal antibodies, such as cixutumumab, may find tumor cells and help carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Octreotide acetate may interfere with the growth of tumor cells and slow the growth of neuroendocrine cancer. Giving cixutumumab together with everolimus and octreotide acetate may be a better treatment for neuroendocrine cancer.

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Identification of grade and origin specific cell populations in serous epithelial ovarian cancer by single cell RNA-seq

Project description:Here we investigated different cell populations within ovarian cancer using single-cell RNA seq: fourteen samples from nine patients with differing grades (high grade, low grade and benign) as well as different origin sites (primary and metastatic tumor site, ovarian in origin and fallopian in origin).

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Wide versus cell type restricted deletion of four tumor suppressor genes determines the type of high grade neuroendocrine lung cancer

Project description:Here we describe novel murine models of High Grade Neuroendocrine Lung Carcinomas driven by the loss of four tumor suppressors: deletion of Rb, PTEN, and p53, in a Rbl1 null background, in a wide variety of lung epithelial cells produces Large Cell Neuroendocrine Carcinoma whereas inactivation of these genes exclusively in basal cells leads to the development of Small Cell Lung Carcinoma, showing that Keratin K5 expressing cells contribute to the development/act as cell of origin of Small Cell Lung Carcinoma differentially influencing the lung cancer type developed. Conditional ablation of Rb1, Trp53 and Pten in pulmonary cells was achieved by intratracheal administration of purified Ad5-CMVcre or Ad5-K5cre (Du Page et al, 2009) to Rb1F/F;Trp53F/F;PtenF/F;Rbl1−/− 8–10 week old mice. Mice were sacrificed 3 to 5 months after the Ad5-cre infection and tumors processed for whole transcriptome analysis. As control animals, RbF/F;p53F/F;PtenF/F;Rbl1−/− littermates were used.

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Distinct Function for ASCL1 and NEUROD1 in Pulmonary Neuroendocrine Tumors (RNA-seq)

Project description:Small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are high-grade pulmonary neuroendocrine tumors. The neural basic helix-loop-helix (bHLH) transcription factors ASCL1 and NEUROD1 have been shown to play crucial roles in promoting the malignant behavior and survival of human SCLC cell lines. In this study, we find ASCL1 and NEUROD1 identify distinct neuroendocrine tumors, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1 and NEUROD1 are often bound in super-enhancers that are associated with highly expressed genes in their respective SCLC cell lines suggesting different cell lineage of origin for these tumors. ASCL1 targets oncogenic genes such as MYCL1, RET, and NFIB, while NEUROD1 targets the oncogenic gene MYC. Although ASCL1 and NEUROD1 regulate different genes, many of these gene targets commonly contribute to neuroendocrine and cell migration function. ASCL1 in particular also regulates genes in the NOTCH pathway and genes important in cell-cycle dynamics. Finally, we demonstrate ASCL1 but not NEUROD1 is required for SCLC and LCNEC tumor formation in current in vivo genetic mouse models of pulmonary neuroendocrine tumors RNA-seq analysis performed on two ASCL1high and two NEUROD1high human SCLC cell lines to identify gene expression patterns in these cells. Also, we performed RNA-seq in mouse neuroendocrine lung tumors obtained from Trp53;Rb1;Rbl2 triple knockout model mice treated with Adeno-CMVCRE intratracheally.

2016-07-21 | E-GEOD-69393 | biostudies-arrayexpress

LncRNA and mRNA expression profiles in High-grade serous ovarian cancer, Low-grade serous ovarian cancer and Normal fallopian tube

Project description:Ovarian cancer is the most lethal gynecologic cancer. High-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype, accounting for three quarters of ovarian cancer. To clarify the changes of gene expression in serous ovarian cancer, we performed lncRNA and mRNA microarrays to identify differentially expressed lncRNAs and mRNAs in High-grade and Low-grade serous ovarian carcinoma compared with Normal fallopian tube.

2020-02-12 | GSE135886 | GEO

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