Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing

García-Chequer, A.J.; Méndez-Tenorio, A.; Olguín-Ruiz, Gabriela Edith; Sánchez-Vallejo, Carlos Javier; Iša, Pavel; Arias, Carlos F.; Torres, Javier; Hernández-Angeles, Adriana; Ramírez‐Ortiz, Marco A.; Lara, Catherine de; Cabrera-Muñoz, M. Lourdes; Sadowinski-Pine, Stanislaw; Bravo-Ortiz, J.C.; Ramón-Garcı́a, Guillermo; Diegopérez-Ramı́rez, Jaime; Ramírez-Reyes, Griselda; Casarrubias-Islas, R.; Ramírez, José Antonio; Orjuela, Manuela; Ponce-Castañeda, M. Verónica

doi:10.1016/j.cancergen.2015.12.001

Cited by 9 publications

(8 citation statements)

References 39 publications

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“…Our results shows heterogeneity in the expression of cluster 17–92, with different levels of expression for members encoded by the same primary transcript, consistent with other reports [46, 47]. Even though some paralog members of cluster 17–92 show high expression levels, including miR-19 which is able to recapitulate the oncogenic activity of the full cluster and is located in a locus previously reported as amplified in Rb [29], they are not expressed in all the samples and do not belong to the 30 miRNA core described previously.…”

Section: Discussionsupporting

confidence: 90%

“…Using annotated data from the miRBase we were able to map in the human genome 2573 out of 2578 miRNAs included in the Affymetrix chip. With a map that we had previously generated using NGS which demonstrated regions of recurrent losses in Rb [ 29 ], we identified in the 995 undetectable miRNAs, those located at loci recurrently lost in Rb by chromosome. In total, we found 144 miRNAs located in areas recurrently lost in Rb [ 37 , 38 ] the complete list is shown in Additional file 3 .…”

Section: Resultsmentioning

confidence: 99%

“…In order to find the chromosomal location for miRNAs, we used annotation data from the miRBase [ 26 ] (at ftp://mirbase.org/pub/mirbase/CURRENT/genomes/ and at http://www.mirdb.org/miRDB/ ). ChromDraw was used to map all miRNAs classified as “Absent” in order to compare their location with respect to chromosomal regions that we had previously reported as regions of recurring loss in Rb [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

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miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma

et al. 2017

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BackgroundmiRNAs exert their effect through a negative regulatory mechanism silencing expression upon hybridizing to their target mRNA, and have a prominent position in the control of many cellular processes including carcinogenesis. Previous miRNA studies on retinoblastoma (Rb) have been limited to specific miRNAs reported in other tumors or to medium density arrays. Here we report expression analysis of the whole miRNome on 12 retinoblastoma tumor samples using a high throughput microarray platform including 2578 mature miRNAs.MethodsTwelve retinoblastoma tumor samples were analyzed using an Affymetrix platform including 2578 mature miRNAs. We applied RMA analysis to normalize raw data, obtained categorical data from detection call values, and also used signal intensity derived expression data. We used Diana-Tools-microT-CDS to find miRNA targets and ChromDraw to map miRNAs in chromosomes.ResultsWe discovered a core-cluster of 30 miRNAs that were highly expressed in all the cases and a cluster of 993 miRNAs that were uniformly absent in all cases. Another 1022 miRNA were variably present in the samples reflecting heterogeneity between tumors. We explored mRNA targets, pathways and biological processes affected by some of these miRNAs. We propose that the core-cluster of 30 miRs represent miRNA machinery common to all Rb, and affecting most pathways considered hallmarks of cancer. In this core, we identified miR-3613 as a potential and critical down regulatory hub, because it is highly expressed in all the samples and its potential mRNA targets include at least 36 tumor suppressor genes, including RB1. In the variably expressed miRNA, 36 were differentially expressed between males and females. Some of the potential pathways targeted by these 36 miRNAs were associated with hormonal production.ConclusionThese findings indicate that Rb tumor samples share a common miRNA expression profile regardless of tumor heterogeneity, and shed light on potential novel therapeutic targets such as mir-3613 This is the first work to delineate the miRNA landscape in retinoblastoma tumor samples using an unbiased approach.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3421-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma

et al. 2017

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“…4b, c ). We also detected eccDNAs from loci reported to frequently undergo gross DNA deletions, such as HLA (5 Mb, 6p21.32–p22.1), KIR (1 Mb, 19q13.42), and SERF1A_SMN2 (2.5 Mb, 5q13.2) 38 , 39 in both blood and muscle (Fig. 3b ; Supplementary Data 3 ).…”

Section: Resultsmentioning

confidence: 87%

Circular DNA elements of chromosomal origin are common in healthy human somatic tissue

Mohiyuddin²,

et al. 2018

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The human genome is generally organized into stable chromosomes, and only tumor cells are known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccDNAs). However, it must be expected that kb eccDNAs exist in normal cells as a result of mutations. Here, we purify and sequence eccDNAs from muscle and blood samples from 16 healthy men, detecting ~100,000 unique eccDNA types from 16 million nuclei. Half of these structures carry genes or gene fragments and the majority are smaller than 25 kb. Transcription from eccDNAs suggests that eccDNAs reside in nuclei and recurrence of certain eccDNAs in several individuals implies DNA circularization hotspots. Gene-rich chromosomes contribute to more eccDNAs per megabase and the most transcribed protein-coding gene in muscle, TTN (titin), provides the most eccDNAs per gene. Thus, somatic genomes are rich in chromosome-derived eccDNAs that may influence phenotypes through altered gene copy numbers and transcription of full-length or truncated genes.

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“…Retinoblastoma (Rb), a rare form of cancer that rapidly develops from the immature cells, or cone precursor cells, of the developing retina, is almost exclusively found in young children, accounting for approximately 3% of all childhood malignancies 17,18. Nevertheless, the mechanism underlying Rb progression remains unclear.…”

Section: Discussionmentioning

confidence: 99%

<p>MicroRNA-188-5p Promotes Epithelial–Mesenchymal Transition by Targeting ID4 Through Wnt/β-catenin Signaling in Retinoblastoma</p>

Yang¹,

Li²,

Wei³

2019

OTT

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Purpose: Here, we investigated the involvement of the miR-188-5p/inhibitor of the DNA binding 4 (ID4) axis in retinoblastoma (Rb). Patients and methods: We included 35 Rb tissues and the corresponding adjacent normal tissues. RT-qPCR, Western blot, lentivirus transfection, measurement of cell migration in vitro, and chip analysis were performed during the study. Mouse Rb models were established to investigate the in vivo mechanisms. Results: We showed that miR-188-5p was upregulated in Rb tissues; moreover, we identified a pathway involving the upregulation of miR-188-5p and its downstream target, ID4, in vitro. Cell experiments revealed that the overexpression of miR-188-5p significantly downregulated the expression of ID4 and the underlying mechanism involved direct targeting of the ID4 3′-UTR. The levels of ID4 are lower in Rb tissues; it plays an antitumor role by inhibiting Rb metastasis in vitro and in vivo. Further investigation revealed that the miR-188-5p/ID4 axis regulated metastasis by promoting epithelial-mesenchymal transition (EMT). We demonstrated that microRNA-188-5p promoted EMT by targeting ID4 through Wnt/β catenin signaling in Rb. Conclusion: miRNA-188-5p can promote EMT by targeting ID4 through the Wnt/β-catenin signaling pathway.

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Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing

Cited by 9 publications

References 39 publications

miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma

miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma

Circular DNA elements of chromosomal origin are common in healthy human somatic tissue

<p>MicroRNA-188-5p Promotes Epithelial–Mesenchymal Transition by Targeting ID4 Through Wnt/β-catenin Signaling in Retinoblastoma</p>

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