Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence (Affymetrix)
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PROVIDER: PRJNA594630 | ENA |
REPOSITORIES: ENA
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Project description:Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence (Exome)
| PRJNA596346 | ENA
Project description:Introduction: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrences. PC is insensitive to conventional chemotherapy, and it would be necessary to reveal the molecular mechanisms of metastasis and develop targeted therapeutics. Methods: We performed the comprehensive whole-exome sequencing (WES) of primary tumors and corresponding normal lung tissues from 14 PC patients (including 4 patients who developed postsurgical distant metastasis) and the RNA sequencing of primary tumors from 6 PC patients (including 4 patients who developed postsurgical distant metastasis). Exon array-based gene expression analysis was performed in 25 PC. Results: We identified a total of 139 alterations in 136 genes. MUC6 and SPTA1 were recurrently mutated with the frequency of 21 % (3/14) and 14% (2/14), respectively. The mucin protein family genes including MUC2, MUC4 and MUC6 were mutated in 36% (5/14) in a mutually exclusive manner. The pathway analysis of mutated genes revealed the enrichment of genes involved in the mitogen-activated protein kinase (MAPK) signaling, regulation of actin cytoskeleton and focal adhesion, and transforming growth factor (TGF)-β signaling pathways. RNA sequencing reveals a total of 8 novel fusion transcripts including one derived from chromosomal translocation between the TRIB2 and PRKCE genes. All the 8 fusion genes were detected in primary PC that had developed metastasis after surgical resection. We identified 14 genes (DENND1B, GRID1, CLMN, DENND1B, NRP1, SEL1L3, C5orf13, TNFRSF21, TES, STK39, MTHFD2, OPN3, MET, and HIST1H3C) up-regulated in 5 PC that had relapsed after surgical resection. Conclusions: In this study we identified novel somatic mutations and chromosomal rearrangements by examining clinically aggressive cases that had developed postsurgical metastasis. It is essential to validate their clinical significance in an independent larger patient cohort.
2020-08-04 | GSE141755 | GEO
Project description:Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence
| PRJNA596184 | ENA
Project description:Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence (RNA)
| PRJNA596178 | ENA
Project description:Introduction: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrences. PC is insensitive to conventional chemotherapy, and it would be necessary to reveal the molecular mechanisms of metastasis and develop targeted therapeutics. Methods: We performed the comprehensive whole-exome sequencing (WES) of primary tumors and corresponding normal lung tissues from 14 PC patients (including 4 patients who developed postsurgical distant metastasis) and the RNA sequencing of primary tumors from 6 PC patients (including 4 patients who developed postsurgical distant metastasis). Exon array-based gene expression analysis was performed in 25 PC. Results: We identified a total of 139 alterations in 136 genes. MUC6 and SPTA1 were recurrently mutated with the frequency of 21 % (3/14) and 14% (2/14), respectively. The mucin protein family genes including MUC2, MUC4 and MUC6 were mutated in 36% (5/14) in a mutually exclusive manner. The pathway analysis of mutated genes revealed the enrichment of genes involved in the mitogen-activated protein kinase (MAPK) signaling, regulation of actin cytoskeleton and focal adhesion, and transforming growth factor (TGF)-β signaling pathways. RNA sequencing reveals a total of 8 novel fusion transcripts including one derived from chromosomal translocation between the TRIB2 and PRKCE genes. All the 8 fusion genes were detected in primary PC that had developed metastasis after surgical resection. We identified 14 genes (DENND1B, GRID1, CLMN, DENND1B, NRP1, SEL1L3, C5orf13, TNFRSF21, TES, STK39, MTHFD2, OPN3, MET, and HIST1H3C) up-regulated in 5 PC that had relapsed after surgical resection. Conclusions: In this study we identified novel somatic mutations and chromosomal rearrangements by examining clinically aggressive cases that had developed postsurgical metastasis. It is essential to validate their clinical significance in an independent larger patient cohort.
2020-08-04 | GSE142190 | GEO
Project description:Introduction: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrences. PC is insensitive to conventional chemotherapy, and it would be necessary to reveal the molecular mechanisms of metastasis and develop targeted therapeutics. Methods: We performed the comprehensive whole-exome sequencing (WES) of primary tumors and corresponding normal lung tissues from 14 PC patients (including 4 patients who developed postsurgical distant metastasis) and the RNA sequencing of primary tumors from 6 PC patients (including 4 patients who developed postsurgical distant metastasis). Exon array-based gene expression analysis was performed in 25 PC. Results: We identified a total of 139 alterations in 136 genes. MUC6 and SPTA1 were recurrently mutated with the frequency of 21 % (3/14) and 14% (2/14), respectively. The mucin protein family genes including MUC2, MUC4 and MUC6 were mutated in 36% (5/14) in a mutually exclusive manner. The pathway analysis of mutated genes revealed the enrichment of genes involved in the mitogen-activated protein kinase (MAPK) signaling, regulation of actin cytoskeleton and focal adhesion, and transforming growth factor (TGF)-β signaling pathways. RNA sequencing reveals a total of 8 novel fusion transcripts including one derived from chromosomal translocation between the TRIB2 and PRKCE genes. All the 8 fusion genes were detected in primary PC that had developed metastasis after surgical resection. We identified 14 genes (DENND1B, GRID1, CLMN, DENND1B, NRP1, SEL1L3, C5orf13, TNFRSF21, TES, STK39, MTHFD2, OPN3, MET, and HIST1H3C) up-regulated in 5 PC that had relapsed after surgical resection. Conclusions: In this study we identified novel somatic mutations and chromosomal rearrangements by examining clinically aggressive cases that had developed postsurgical metastasis. It is essential to validate their clinical significance in an independent larger patient cohort.
2020-08-04 | GSE142186 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-08-04 | GSE142191 | GEO
Project description:Affymetrix GeneChip miRNA 4.0 Array for meningioma recurrence profilling
| PRJNA522376 | ENA
Project description:Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors.We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, typical and atypical carcinoid, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum. Pathway analysis of of CNV and gene expression data suggested deregulation of the NF-ĸB and MAPK/ERK pathways. This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors.
2018-01-26 | GSE108055 | GEO
Project description:Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with = 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. Keywords: Autism spectrum disorder, Affymetrix SNP genotyping, linkage analysis, copy number analysis, chromosomal rearrangements.
2007-02-20 | GSE6754 | GEO