Loss of Heterozygosity on Chromosome 11p15.5 and Relapse in Hepatoblastomas

Chitragar, Sanjeev; Iyer, Venkateswaran K.; Agarwala, Sandeep; Gupta, Siddhartha Dutta; Sharma, Ashwani; Wari, Mohammad Nahidul

doi:10.1055/s-0030-1267208

Cited by 13 publications

(12 citation statements)

References 11 publications

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“…The most common sites for gene and epigenetic changes are 11p15.5 and 20q13.3. H19 and IGF2, which are closely related to tumors, are located in the 11p15.5 region [21,67].…”

Section: Regulation Of Dna Methylation Of Imprinted Genesmentioning

confidence: 99%

DNA methylation in Hepatoblastoma-a literature review

Shen

Zhang

et al. 2020

Ital J Pediatr

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Hepatoblastoma (HB) is the most common malignant liver tumor in children. Abnormal activation of the Wnt/βcatenin signaling pathway plays an important role in the formation and development of HB. Genes in HB show a global hypomethylation change, accompanied by hypermethylation of specific tumor suppressor genes (TSGs). This article reviews the hypermethylation changes in several TSGs, such as RASSF1A, SOCS1, APC, HHIP, and P16, and analyzes the pathways and mechanisms of TSGs regulating gene expression. The role of the methylation-regulating enzymes DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) family members enzymes in the methylation changes of HB was analyzed, and it was speculated that the occurrence of HB is partly due to the obstruction of liver differentiation in the early stage of differentiation. The origin cells may be incompletely differentiated hepatocytes remaining in the liver of children after birth. Therefore, further studying the role of methylation regulating enzymes in methylation changes in HB is a promising future research direction.

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“…The most common sites for gene and epigenetic changes are 11p15.5 and 20q13.3. H19 and IGF2, which are closely related to tumors, are located in the 11p15.5 region [21,67].…”

Section: Regulation Of Dna Methylation Of Imprinted Genesmentioning

confidence: 99%

DNA methylation in Hepatoblastoma-a literature review

Shen

Zhang

et al. 2020

Ital J Pediatr

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“…The hypermethylation leading to biallelic expression of IGF2 is seen in a range of tumors, also including hepatoblastoma [6,7]. The LOH of 11p15.5, especially the loss of the maternal allele, is found in approximately 20% of hepatoblastoma cases, and it is reported to be a risk factor for the relapse of this tumor [7,8]. Furthermore, several imprinted genes are overexpressed in hepatoblastoma as mentioned above.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

et al. 2013

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BackgroundAberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors.MethodsThe methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms.ResultsAmong 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations.ConclusionsOur analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma.

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“…Hepatocellular carcinoma [34] Hepatoblastoma [35] Glioblastoma [36] Bladder cancer [37] Breast cancer [38] Pancreatic carcinoma [39] Tongue carcinoma [40] Osteosarcoma [41] Acute myeloid leukemia [42] Rhabdomyosarcoma [43] Esophageal cancer [44] Ewing sarcoma [45] Colorectal cancer [46] Pleural solitary fibrous tumors [47] Endometrial cancer [48] Ovarian cancer [49] Adrenocortical tumors [50] Prostate cancer [51] (x)* reference for listed cancer types.…”

Section: Figurementioning

confidence: 99%

“…Although LOH has been mainly observed in both translocation-negative and -positive RMS, LOH of the 11p15.5 locus was identified as an early driving alteration in fusion-negative RMS [125]. LOH of the locus has also been reported in Wilms tumor [123] and hepatoblastomas [35].…”

Section: Overexpression Of Igf2 In Cancermentioning

confidence: 99%

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Röttgering¹,

Szuhai²

2019

obm genet

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Insulin-like growth factor 2 (IGF2) is a strong mitogenic peptide with an imprinted gene that is primarily involved in fetal development. It is highly expressed in the fetus where it is involved in fetal growth and tissue differentiation. However, postnatally, the expression of IGF2 decreases despite higher expression levels in the blood as compared with that of IGF1. In adults, the physiological function of IGF2 is poorly understood; however, the possibility of a metabolic function exists. Although the expression of IGF2 normally decreases in adults, it is overexpressed in a variety of cancers and associated with increased insulin-like growth factor 1 (IGF1R) receptor and insulin receptor (IR) activity. This subsequently increases the activity of downstream genes such as AKT, FOXO, and MAPK, resulting in enhanced proliferation, survival, and overall worse prognosis in patients overexpressing IGF2. As IGF1R activation has been found in several types of cancers, many different IGF1R-targeted therapies have been clinically evaluated, however, with only limited anti-cancer efficacy. In the present review, the physiological function of IGF2 will be outlined in relation to gene expression, imprinting, and signaling. Additionally, differences in physiological and aberrant signaling of IGF2 in cancer will be summarized.

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Loss of Heterozygosity on Chromosome 11p15.5 and Relapse in Hepatoblastomas

Cited by 13 publications

References 11 publications

DNA methylation in Hepatoblastoma-a literature review

DNA methylation in Hepatoblastoma-a literature review

Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

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