Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma

Li, Meng; Zhao, Hong; Zhang, Xiaosong; Wood, Laura D.; Anders, Robert A.; Choti, Michael A.; Pawlik, Timothy M.; Daniel, Hubert Darius J.; Kannangai, Rajesh; Offerhaus, G. Johan A.; Velculescu, Victor E.; Wang, Linfang; Zhou, Shibin; Vogelstein, Bert; Hruban, Ralph H.; Papadopoulos, Nick; Cai, Jianqiang; Torbenson, Michael; Kinzler, Kenneth W.

doi:10.1038/ng.903

Cited by 384 publications

(310 citation statements)

References 13 publications

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“…Grasso et al 47 also described a frequent copy number loss on chromosome 5q21 at the location of CHD1, a gene encoding a chromatinremodeling enzyme, and documented loss or mutation in multiple chromatin-remodeling genes, as has been found for multiple tumor types. 47,[52][53][54] They documented that multiple of these chromatinmodifying genes directly interact with the androgen receptor and along with additional regulators, such as FOXA1, can partially explain the androgen-resistant nature of the tumors they sequenced.…”

Section: Somatic Alterations In Tumorsmentioning

confidence: 99%

Genetics and genomics of prostate cancer

Dean¹,

Li²

2013

Asian J Androl

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Prostate cancer (PCa) is one of the most common malignancies in the world with over 890 000 cases and over 258 000 deaths worldwide each year. Nearly all mortalities from PCa are due to metastatic disease, typically through tumors that evolve to be hormone-refractory or castrate-resistant. Despite intensive epidemiological study, there are few known environmental risk factors, and age and family history are the major determinants. However, there is extreme heterogeneity in PCa incidence worldwide, suggesting that major determining factors have not been described. Genome-wide association studies have been performed and a considerable number of significant, but low-risk loci have been identified. In addition, several groups have analyzed PCa by determination of genomic copy number, fusion gene generation and targeted resequencing of candidate genes, as well as exome and whole genome sequencing. These initial studies have examined both primary and metastatic tumors as well as murine xenografts and identified somatic alterations in TP53 and other potential driver genes, and the disturbance of androgen response and cell cycle pathways. It is hoped that continued characterization of risk factors as well as gene mutation and misregulation in tumors will aid in understanding, diagnosing and better treating PCa.

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Section: Somatic Alterations In Tumorsmentioning

confidence: 99%

Genetics and genomics of prostate cancer

Dean¹,

Li²

2013

Asian J Androl

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“…Multiple studies have revealed etiological patterns and multiple genes/pathways signifying initiation and progression of HCC. These pathways include CTNNB1/WNT‐β‐catenin, TPp53, ARID1/2s, HGF/c‐Met, and vascular endothelial growth factor/angiogenic signaling 5, 6, 7, 8, 9, 10, 11, 12. However, unlike the transforming growth factor β (TGF‐β) pathway, loss of p53 and/or activation of β‐catenin do not spontaneously drive HCC in animal models 13, 14, 15…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor‐β in liver cancer stem cells and regeneration

Rao

Zaidi

Banerjee

et al. 2017

Hepatology Communications

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Cancer stem cells have established mechanisms that contribute to tumor heterogeneity as well as resistance to therapy. Over 40% of hepatocellular carcinomas (HCCs) are considered to be clonal and arise from a stem‐like/cancer stem cell. Moreover, HCC is the second leading cause of cancer death worldwide, and an improved understanding of cancer stem cells and targeting these in this cancer are urgently needed. Multiple studies have revealed etiological patterns and multiple genes/pathways signifying initiation and progression of HCC; however, unlike the transforming growth factor β (TGF‐β) pathway, loss of p53 and/or activation of β‐catenin do not spontaneously drive HCC in animal models. Despite many advances in cancer genetics that include identifying the dominant role of TGF‐β signaling in gastrointestinal cancers, we have not reached an integrated view of genetic mutations, copy number changes, driver pathways, and animal models that support effective targeted therapies for these common and lethal cancers. Moreover, pathways involved in stem cell transformation into gastrointestinal cancers remain largely undefined. Identifying the key mechanisms and developing models that reflect the human disease can lead to effective new treatment strategies. In this review, we dissect the evidence obtained from mouse and human liver regeneration, and mouse genetics, to provide insight into the role of TGF‐β in regulating the cancer stem cell niche. (Hepatology Communications 2017;1:477–493)

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“…In the United States and Europe, 18.2% of HCV-associated HCC cases were identified with ARID2-inactivating mutations. [4] However, studies have also reported mutation frequencies of approximately 5-10% for ARID2 in HCC and truncation of ARID2 leads to loss of protein function and chromatin dysregulation. [4,11,12] With the development of whole-genome sequencing technology, the next generation sequencing of genome DNA provides the possibility that more novel genetic and genomic alterations may be discovered and may provide new insights for understanding the pathogenesis of HCC.…”

Section: Somatic Mutationmentioning

confidence: 99%

“…[4] However, studies have also reported mutation frequencies of approximately 5-10% for ARID2 in HCC and truncation of ARID2 leads to loss of protein function and chromatin dysregulation. [4,11,12] With the development of whole-genome sequencing technology, the next generation sequencing of genome DNA provides the possibility that more novel genetic and genomic alterations may be discovered and may provide new insights for understanding the pathogenesis of HCC. However, several recent studies using next generation sequencing for analysis of mutation in HCC showed that the most frequent mutations with mutated rate over 10% were mainly genes reported previously such as TP53, β-catenin, and genes of chromatin-remodeling complex such as AT-rich interactive domain 1A (ARID1A) (14/110).…”

Section: Somatic Mutationmentioning

confidence: 99%

“…[2][3][4] Other mutated genes such as SMAD2/SMAD4 in the transforming growth factor beta (TGF-β) pathway, caspase 8 (CASP8), and Kruppel-like factor 6 were identified with mutation frequency around 10% in HCC, [5][6][7] while most other mutated genes were identified with relatively low frequency of < 10% in HCC. [2] Germline mutations in the TP53 gene have been identified in patients with Li-Fraumeni syndrome, which is an inherited cancer predisposition syndrome characterized by a wide spectrum of neoplasms.…”

Section: Somatic Mutationmentioning

confidence: 99%

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Recent updates of genetic and genomic alterations in hepatocellular carcinoma

Zhao¹,

Huang²

2015

Hepatoma Res

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Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. However, the molecular mechanisms underlining the development and progression of HCC remain unclear. Genetic and genomic alterations are common events in various types of cancers including HCC. With the development and application of next generation sequencing technology, novel genetic and genomic alterations in HCC have been identified. Here, the article reviews recent updates on the genetic and genomic alterations in HCC.

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Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma

Cited by 384 publications

References 13 publications

Genetics and genomics of prostate cancer

Genetics and genomics of prostate cancer

Transforming growth factor‐β in liver cancer stem cells and regeneration

Recent updates of genetic and genomic alterations in hepatocellular carcinoma

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