Upregulated Genes at 2q24 Gains as Candidate Oncogenes in hepatoblastomas

Rodrigues, T.; Fidalgo, Felipe; Costa, Cecília Maria Lima da; Ferreira, Elisa Napolitano; Cunha, Isabela Werneck da; Carraro, Dirce Maria; Krepischi, Ana Cristina Victorino; Rosenberg, Carla

doi:10.2217/fon.14.149

Cited by 25 publications

(23 citation statements)

References 47 publications

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“…It was found that DAPL1 gene was downregulated in an in vitro cultured ovarian granulosa cell of pig [22], but upregulated in the endometrial stromal and epithelial cells under the treatment of lipopolysaccharide [23]. DAPL1 gene was found to be upregulated in nine hepatoblastomas patients [24]. Based on the expression dataset of TCGA-LIHC (Liver hepatocellular carcinoma) cohort, we also observed an enhanced DAPL1 gene expression in hepatocellular carcinoma tissues, compared to normal tissues (data not shown).…”

Section: Discussionmentioning

confidence: 81%

WITHDRAWN: Identification of death-associated protein-like 1 (DAPL1) as a novel prognostic biomarker of breast cancer

Zhang

Liang

2020

Preprint

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Background: It is meaningful to identify the potential clinical prognosis-associated oncogenes for cases with breast cancer, considering the complicated pathogenesis of breast cancer.Methods: We first utilized the bioinformatics approach to investigate the role of the DAPL1 (death-associated protein-like 1) in breast cancer, based on the available datasets of TCGA and GEO.Results: DAPL1 is lowly expressed in breast cancer tissues compared with the normal tissues. For the breast cancer cases of the TCGA-BRCA cohort, we observed a correlation between lowly expressed DAPL1 gene and poor clinical prognosis of overall survival ( P =0.0028). Based on the survival data of GEO, the low DAPL1 expression was associated with a poor prognosis of distant metastasis free survival ( P =0.0023), and relapse free survival ( P =0.0065). DAPL1 expression was linked to the mutation status or copy number variation o f several genes, such as MAP3K1 , NUP98 , and CCDC59. The infiltration level of immune cells (e.g., M1 macrophage, Follicular B helper T cells, etc.) may be involved in the etiology of breast cancer. Based on the DAPL1 -correlated genes, GSEA, GO, and KEGG analysis data indicated the association between DAPL1 expression and a series of biological issues, such as DNA packaging complex, DNA repair complex, nucleotide excision repair, ubiquitin-like protein binding, and ubiquitin proteasome pathway. We also identified several DAPL1 -associated phosphorylation kinases, such as MAPK, PRKACA, and GSK3B.Conclusions: DAPL1 gene is first identified as a prognosis biomarker of breast cancer, and the underlying molecular mechanism involves protein phosphorylation, immune cell infiltration, and DNA repair or protein ubiquitin-associated cellular pathways.

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Section: Discussionmentioning

confidence: 81%

WITHDRAWN: Identification of death-associated protein-like 1 (DAPL1) as a novel prognostic biomarker of breast cancer

Zhang

Liang

2020

Preprint

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“…However, focusing on the analysis of individual CpGs, hepatoblastomas from both sets showed a slightly hypomethylated pattern only at the first CpG of the LINE-1 sequence when compared with the differentiated livers (p = 0.03802 for set #1 and p = 0.05174 for set #2; Figure 4 ). The copy number alteration profile for all samples of hepatoblastoma set #1 has been previously evaluated by array-CGH [ 32 ]; tumor samples with and without chromosomal alterations >100 kb were compared with control differentiated livers regarding the methylation levels of LINE-1. Significant differences in LINE-1 methylation levels were found again only for the first CpG site ( Supplementary Figure 3 ), which is slightly hypomethylated in hepatoblastomas with copy number alterations (p = 0.0057; the Kruskall-Wallis test also indicated a difference of p = 0.0166 between the groups at this CpG).…”

Section: Resultsmentioning

confidence: 99%

DNA methylation landscape of hepatoblastomas reveals arrest at early stages of liver differentiation and cancer-related alterations

et al. 2016

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Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas). In comparison to differentiated livers, hepatoblastomas exhibited a widespread and non-stochastic pattern of global low-level hypomethylation. The analysis revealed 1,359 differentially methylated CpG sites (DMSs) between hepatoblastomas and control livers, which are associated with 765 genes. Hypomethylation was detected in hepatoblastomas for ~58% of the DMSs with enrichment at intergenic sites, and most of the hypermethylated CpGs were located in CpG islands. Functional analyses revealed enrichment in signaling pathways involved in metabolism, negative regulation of cell differentiation, liver development, cancer, and Wnt signaling pathway. Strikingly, an important overlap was observed between the 1,359 DMSs and the CpG sites reported to exhibit methylation changes through liver development (p<0.0001), with similar patterns of methylation in both hepatoblastomas and fetal livers compared to adult livers. Overall, our results suggest an arrest at early stages of liver cell differentiation, in line with the hypothesis that hepatoblastoma ontogeny involves the disruption of liver development. This genome-wide methylation dysfunction, taken together with a relatively small number of driver genetic mutations reported for both adult and pediatric liver cancers, shed light on the relevance of epigenetic mechanisms for hepatic tumorigenesis.

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“…Using our non‐synonymous, rare variant prioritization strategy, a second variant was identified in GALNT5 . Literature review provided no evidence that this variant was contributing to the disease presentation, as the gene has only previously been associated with differing expression in pancreatic, liver, and gastric cancers (Caffrey et al, 2019; Guo et al, 2018; Rodrigues et al, 2014). In addition, although this variant was considered rare (MAF < 1%), it had been previously reported in the homozygous state in multiple individuals in the gnomAD database (v2.1.1 and v3).…”

Section: Discussionmentioning

confidence: 99%

A novel homozygous variant in REN in a family presenting with classic features of disorders involving the renin–angiotensin pathway, without renal tubular dysgenesis

Dilliott

Wang

Brown

et al. 2020

American J of Med Genetics Pt A

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Autosomal recessively inherited pathogenic variants in genes associated with the renin–angiotensin–aldosterone system (RAAS) result in early onset oligohydramnios and clinical features of the Potter sequence, typically in association with proximal renal tubules dysgenesis. We describe two siblings and a first cousin who had severe oligohydramnios in the second trimester, and presented at birth with loose skin, wide fontanelles and sutures, and pulmonary insufficiency. Two had refractory hypotension during their brief lives and one received palliative care after birth. All were found to have a homozygous nonsense variant, REN: c.891delG; p.Tyr287*, on exome sequencing. Autopsy limited to the genitourinary system in two of the children revealed normal renal tubular histology in both. Immunoblotting confirmed diminished expression of renin within cultured skin fibroblasts. To our knowledge, this is the first identification of an association between biallelic variants in REN and oligohydramnios in the absence of renal tubular dysgenesis. Due to its role in the RAAS, it has previously been proposed that the decreased expression of REN results in hypotension, ischemia, and decreased urine production. We suggest sequencing of genes in the RAAS, including REN, should be considered in cases of severe early onset oligohydramnios, even when renal morphology and histology are normal.

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Upregulated Genes at 2q24 Gains as Candidate Oncogenes in hepatoblastomas

Abstract: These genes appear as candidates for hepatoblastoma tumorigenesis.

Cited by 25 publications

References 47 publications

WITHDRAWN: Identification of death-associated protein-like 1 (DAPL1) as a novel prognostic biomarker of breast cancer

WITHDRAWN: Identification of death-associated protein-like 1 (DAPL1) as a novel prognostic biomarker of breast cancer

DNA methylation landscape of hepatoblastomas reveals arrest at early stages of liver differentiation and cancer-related alterations

A novel homozygous variant in REN in a family presenting with classic features of disorders involving the renin–angiotensin pathway, without renal tubular dysgenesis

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