Clinical significance of loss of heterozygosity for M6P/IGF2R in patients with primary hepatocellular carcinoma

Jang, Hong Seok; Kang, Ki Mun; Choi, Byung Ock; Chai, Gyu Young; Hong, Soon Chan; Ha, Woo Song; Jirtle, Randy L.

doi:10.3748/wjg.14.1394

Cited by 19 publications

(11 citation statements)

References 27 publications

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“…For example, LOH in the genes ARD1 homolog B ( S. cerevisiae ) ( ARD1B ) and Mus musculus septin 11 ( SEPT11 ) were found to be significant prognostic factors for poor OS[63], and LOH in mannose 6-phosphate/insulin-like growth factor 2 receptor ( M6P/IGF2R ) was found to be predictive of poor clinical outcomes in surgically resected primary HCC patients[64]. …”

Section: Genomic Instabilitymentioning

confidence: 99%

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

137

108

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.

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Section: Genomic Instabilitymentioning

confidence: 99%

Genetic alterations in hepatocellular carcinoma: An update

Niu¹,

Niu²,

Wang³

2016

WJG

137

108

View full text Add to dashboard Cite

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“…Interestingly, overactivation of the IGF axis is a peculiar trait in at least one fifth of the cases of HCC and a composite series of molecular events including IGF-2R allelic loss, epigenetically driven IGF-2 reactivation, and downregulation of the IGF-binding proteins characterizes this peculiar subfamily of tumors. 132 Some of these molecular events such as loss of heterozygosity of the IGF-2R gene, 133 IGF-2 promoter hypomethylation 134 are adverse prognostic features, whereas conserved expression of IGF-binding protein 3 is associated with better survival in HCC. 135 …”

Section: Insulin-like Growth Factormentioning

confidence: 99%

Tissue Biomarkers of Prognostic Significance in Hepatocellular Carcinoma

Pinato

Pirisi

Maslen

et al. 2014

Advances in Anatomic Pathology

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Despite major advancements in the clinical management of hepatocellular carcinoma (HCC), the natural history of this disease is characterized by an invariably poor prognosis. However, there are significant interindividual variations in the biologic behavior of this tumor and this combined with the confounding effect of liver function on patient survival makes prognostic prediction particularly difficult. Several studies have attempted to investigate the prognostic role of tissue biomarkers to better understand the molecular basis of HCC progression. These studies have looked at several aspects of cancer biology including proliferative potential, invasive capacity, and angiogenic promotion utilizing different methodologies. The aim of this review is to summarize the role of tissue biomarkers in the prognostic prediction of HCC and to outline questions and strategies in the prognostic assessment of HCC.

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“…Nevertheless, this conclusion has also been called into question [140]. Heterozygosity at the IGF-II/M6P receptor locus due to the loss of one allele and somatic mutations in the remaining allele have also been associated with a variety of cancers [141, 142]. Additionally, microsatellite instability within the IGF-II/M6P receptor gene has been shown to occur in a large number of gastrointestinal cancers [143], and single-nucleotide polymorphisms within the receptor gene have been suggested to increase the risk of developing cancers [144].…”

Section: Functions Of the Igf-ii/m6p Receptormentioning

confidence: 99%

Insulin-Like Growth Factor-II/Cation-Independent Mannose 6-Phosphate Receptor in Neurodegenerative Diseases

et al. 2016

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The insulin-like growth factor II/mannose 6-phosphate (IGF-II/M6P) receptor is a multifunctional single-transmembrane glycoprotein. Recent studies have advanced our understanding of the structure, ligand binding properties and trafficking of the IGF-II/M6P receptor. This receptor has been implicated in a variety of important cellular processes including growth and development, clearance of IGF-II, proteolytic activation of enzymes and growth factor precursors, in addition to its well-known role in the delivery of lysosomal enzymes. The IGF-II/M6P receptor, distributed widely in the central nervous system, has additional roles in mediating neurotransmitter release and memory enhancement/consolidation, possibly through activating IGF-II-related intracellular signaling pathways. Recent studies suggest that overexpression of the IGF-II/M6P receptor may have an important role in regulating the levels of transcripts and proteins involved in the development of Alzheimer’s disease (AD) – the prevalent cause of dementia affecting the elderly population in our society. It is reported that IGF-II/M6P receptor overexpression can increase the levels/processing of amyloid precursor protein leading to the generation of β-amyloid peptide, which is associated with degeneration of neurons and subsequent development of AD pathology. Given the significance of the receptor in mediating the transport and functioning of the lysosomal enzymes, it is being considered for therapeutic delivery of enzymes to the lysosomes to treat lysosomal storage disorders. Notwithstanding these results, additional studies are required to validate and fully characterize the function of the IGF-II/M6P receptor in the normal brain and its involvement in various neurodegenerative disorders including AD. It is also critical to understand the interaction between the IGF-II/M6P receptor and lysosomal enzymes in neurodegenerative processes, which may shed some light on developing approaches to detect and prevent neurodegeneration through the dysfunction of the receptor and the endosomal-lysosomal system.

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Clinical significance of loss of heterozygosity for M6P/IGF2R in patients with primary hepatocellular carcinoma

Cited by 19 publications

References 27 publications

Genetic alterations in hepatocellular carcinoma: An update

Genetic alterations in hepatocellular carcinoma: An update

Tissue Biomarkers of Prognostic Significance in Hepatocellular Carcinoma

Insulin-Like Growth Factor-II/Cation-Independent Mannose 6-Phosphate Receptor in Neurodegenerative Diseases

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