Similar Datasets
Project description:Since ESCC is a complex and heterogeneous disease, it is increasingly important that analyses combine the evaluation of alterations in DNA, including somatic copy number alterations (SCNA), which distinguished from germ line copy number variants, allelic imbalance and LOH, and RNA, including those that occur in both mRNA and miRNA on the same specimen. Thus, in order to better understand their potential interactions in the development of cancers, in the present study, we studied alterations at DNA level as well as expression of mRNA and target miRNA in tumors and their matched normal tissues from 56 ESCC cases on a candidate tumor suppressor gene CSMD1 to characterize there alterations in this gene for import insights into the cellular detect that cause the complex disease, ESCC.
2018-10-31 | GSE74704 | GEO
Project description:Since ESCC is a complex and heterogeneous disease, it is increasingly important that analyses combine the evaluation of alterations in DNA, including somatic copy number alterations (SCNA), which distinguished from germ line copy number variants, allelic imbalance and LOH, and RNA, including those that occur in both mRNA and miRNA on the same specimen. Thus, in order to better understand their potential interactions in the development of cancers, in the present study, we studied alterations at DNA level as well as expression of mRNA and target miRNA in tumors and their matched normal tissues from 56 ESCC cases on a candidate tumor suppressor gene CSMD1 to characterize there alterations in this gene for import insights into the cellular detect that cause the complex disease, ESCC.
2018-10-31 | GSE74703 | GEO
Project description:CSMD1 shows complex somatic alterations in esophageal squamous cell carcinoma based on a pilot integrated analysis
| PRJNA301209 | ENA
Project description:BackgroundHuman Cub and Sushi Multiple Domains 1 (CSMD1) is a novel candidate tumor-suppressor gene that codes for multiple domains, including complement regulatory and adhesion proteins, and has recently been shown to have alterations in multiple cancers. We investigated CSMD1 in esophageal squamous cell carcinoma (ESCC) by performing an integrated analysis on somatic copy number alterations (CNAs), including copy-number gain or loss, allelic imbalance (AI), loss of heterozygosity (LOH), and the expressions of mRNA and its target miRNAs on specimens from the same patients with ESCC.Results(i) Two-thirds of ESCC patients had all three types of alterations studied-somatic DNA alterations in 70%, and abnormal expressions of CSMD1 RNA in 69% and in target miRNAs in 66%; patterns among these alterations were complex. (ii) In total, 97% of 888 CSMD1 SNPs studied showed somatic DNA alterations, with most located near exons 4-11, 24-25, 39-40, 55-56, and 69-70. (iii) In total, 68% of SNPs with a CNA were correlated with expression of CSMD1. (iv) A total of 33 correlations between non-coding SNPs and expression of CSMD1 target miRs were found.ConclusionsOur results indicate that the CSMD1 gene may play a role in ESCC through complex patterns of DNA alterations and RNA and miRNA expressions. Alterations in some somatic SNPs in non-coding regions of CSMD1 appear to influence expression of this gene and its target miRNAs.
| S-EPMC9599939 | biostudies-literature
Project description:Gastric cancer and esophageal cancer are the second and sixth leading causes of cancer-related death worldwide. Multiple genomic alterations underlying gastric cancer and esophageal squamous cell carcinoma (ESCC) have been identified, but the full spectrum of genomic structural variations and mutations have yet to be uncovered. Here, we report the results of whole-genome sequencing of 30 samples comprising tumor and blood from 15 patients, four of whom presented with ESCC, seven with gastric cardia adenocarcinoma (GCA), and four with gastric noncardia adenocarcinoma. Analyses revealed that an A>C mutation was common in GCA, and in addition to the preferential nucleotide sequence of A located 5 prime to the mutation as noted in previous studies, we found enrichment of T in the 5 prime base. The A>C mutations in GCA suggested that oxidation of guanine may be a potential mechanism underlying cancer mutagenesis. Furthermore, we identified genes with mutations in gastric cancer and ESCC, including well-known cancer genes, TP53, JAK3, BRCA2, FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including MACROD2, FHIT, and PARK2 that were often intragenic deletions. These structural alterations were validated using the The Cancer Genome Atlas dataset. Our studies provide new insights into understanding the genomic landscape, genome instability, and mutation profile underlying gastric cancer and ESCC development. Cancer Res; 76(7); 1714-23. ©2016 AACR.
| S-EPMC4873357 | biostudies-literature
Project description:The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC.
| S-EPMC5244375 | biostudies-literature
Project description:Gastric cancer and esophageal cancer are the 2nd and 6th leading causes of cancer death worldwide. We analyzed DNA copy numbers for 73 ESCC (43 SNP5.0 and 30 500K SNP) with the Affymetrix SNP arrays . Our analyses implicated potential driver mutations involving the following genes: mutations in TP53, BRCA2, NOTCH2, CTNNB1, and LEPREL2; amplification of CCND1, FGF3/4/19, and MYC; and deletion of CDKN2A/B.
2016-05-09 | GSE43470 | GEO
Project description:Lung squamous cell carcinoma (LUSC) is the most common cause of global cancer-related mortality and the major risk factors is smoking consumption. By analyzing ∼500 LUSC samples from The Cancer Genome Atlas, we detected a higher mutational burden as well as a higher level of methylation changes in younger patients. The SNPs mutational profiling showed enrichments of smoking-related signature 4 and defective DNA mismatch repair (MMR)-related signature 6 in younger patients, while the defective DNA MMR signature 26 was enriched among older patients. Furthermore, gene set enrichment analysis was performed in order to explore functional effect of somatic alterations in relation to patient age. Extracellular Matrix-Receptor Interaction, Nucleotide Excision Repair and Axon Guidance seem crucial disrupted pathways in younger patients. We hypothesize that a higher sensitivity to smoking-related damages and the enrichment of defective DNA MMR related mutations may contribute to the higher mutational burden of younger patients. The two distinct age-related defective DNA MMR signatures 6 and 26 might be crucial mutational patterns in LUSC tumorigenesis which may develop distinct phenotypes. Our study provides indications of age-dependent differences in mutational backgrounds (SNPs and CNVs) as well as epigenetic patterns that might be relevant for age adjusted treatment approaches.
| S-EPMC6114948 | biostudies-literature
Project description:BackgroundEsophageal squamous cell carcinomas (ESCC) is the fourth most lethal cancer in China. Previous studies reveal several highly conserved mutational processes in ESCC. However, it remains unclear what are the true regulators of the mutational processes.ResultsWe analyzed the somatic mutational signatures in 302 paired whole-exome sequencing data of ESCC in a Chinese population for potential regulators of the mutational processes. We identified three conserved subtypes based on the mutational signatures with significantly different clinical outcomes. Our results show that patients of different subpopulations of Chinese differ significantly in the activity of the "NpCpG" signature (FDR = 0.00188). In addition, we report ZNF750 and CDC27, of which the somatic statuses and the genetic burdens consistently influence the activities of specific mutational signatures in ESCC: the somatic ZNF750 status is associated with the AID/APOBEC-related mutational process (FDR = 0.0637); the somatic CDC27 copy-number is associated with the "NpCpG" (FDR = 0.00615) and the AID/APOBEC-related mutational processes (FDR = 8.69 × 10- 4). The burdens of germline variants in the two genes also significantly influence the activities of the same somatic mutational signatures (FDR < 0.1).ConclusionsWe report multiple factors that influence the mutational processes in ESCC including: the subpopulations of Chinese; the germline and somatic statuses of ZNF750 and CDC27 and exposure to alcohol and tobacco. Our findings based on the evidences from both germline and somatic levels reveal potential genetic regulators of the somatic mutational processes and provide insights into the biology of esophageal carcinogenesis.
| S-EPMC6048762 | biostudies-literature
Project description:Esophageal cancer has a strikingly low survival rate mainly due to the lack of diagnostic markers for early detection and effective therapies. In the U.S., 75% of individuals diagnosed with esophageal squamous cell carcinoma (ESCC) are of African descent. African American ESCC (AA ESCC) is particularly aggressive, and its biological underpinnings remain poorly understood. We sought to identify the genomic abnormalities by conducting whole exome sequencing of 10 pairs of matched AA esophageal squamous cell tumor and control tissues. Genomic analysis revealed diverse somatic mutations, copy number alterations (SCNAs), and potential cancer driver genes. Exome variants created two subgroups carrying either a high or low tumor mutation burden. Somatic mutational analysis based on the Catalog of Somatic Mutations in Cancer (COSMIC) detected SBS16 as the prominent signature in the high mutation rate group suggesting increased DNA damage. SBS26 was also detected, suggesting possible defects in mismatch repair and microsatellite instability. We found SCNAs in multiple chromosome segments, encoding MYC on 8q24.21, PIK3CA and SOX2 on 3q26, CCND1, SHANK2, CTTN on 11q13.3, and KRAS on 12p12. Amplifications of EGFRvIII and EGFRvIVa mutants were observed in two patients, representing a novel finding in ESCC that has potential clinical relevance. This present exome sequencing, which to our knowledge, represents the first comprehensive exome analysis exclusively in AA ESCC, and highlights novel mutated loci that might explain the aggressive nature of AA ESCC and lead to the development of diagnostic and prognostic markers as well as therapeutic targets.
| S-EPMC8292420 | biostudies-literature