Integrated Analysis of Whole Genome and Transcriptome Sequencing Reveals Diverse Transcriptomic Aberrations Driven by Somatic Genomic Changes in Liver Cancers

Shiraishi, Yuichi; Fujimoto, Akihiro; Furuta, Mayuko; Tanaka, Hiroko; Chiba, Kenichi; Boroevich, Keith A.; Abe, Tetsuo; Kawakami, Yoshiiku; Ueno, Masaki; Gotoh, Kunihito; Ariizumi, Shun‐ichi; Shibuya, Tetsuo; Nakano, Kaoru; Sasaki, Aya; Maejima, Kazuhiro; Kitada, Rina; Hayami, Shinya; Shigekawa, Yoshinobu; Marubashi, Shigeru; Yamada, Terumasa; Kubo, Michiaki; Ishikawa, Osamu; Aikata, Hiroshi; Arihiro, Koji; Ohdan, Hideki; Yamamoto, Masakazu; Yamaue, Hiroki; Chayama, Kazuaki; Tsunoda, Tatsuhiko; Miyano, Satoru; Nakagawa, Hidewaki

doi:10.1371/journal.pone.0114263

Cited by 76 publications

(73 citation statements)

References 39 publications

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“…A recent study also shows that the PBAF remodeling complex is important for doublestrand breaks (DSBs)-induced transcriptional silencing and promotes repair of a subset of DNA DSBs at early time points [48]. ARID2 has been recently identified as a key cancer gene for hepatocellular carcinoma [49,50], melanoma [51,52], and lung cancer [53]. Recently, a missense mutation R314C in ARID2 was reported in an individual with autism [54].…”

Section: Resultsmentioning

confidence: 99%

Mutations in ARID2 are associated with intellectual disabilities

Shang

Cho²,

Retterer³

et al. 2015

Neurogenetics

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The etiology of intellectual disabilities (ID) remains unknown for the majority of patients. Due to reduced reproductive fitness in many individuals with ID, de novo mutations account for a significant portion of severe ID. The ATP-dependent SWI/SNF chromatin modifier has been linked with neurodevelopmental disorders including ID and autism. ARID2 is an intrinsic component of polybromo-associated BAF (PBAF), the SWI/SNF subcomplex. In this study, we used clinical whole exome sequencing (WES) in proband-parent-trios to identify the etiology of ID. We identified four independent, novel, loss of function variants in ARID2 gene in four patients, three of which were confirmed to be de novo. The patients all have ID and share other clinical characteristics including attention deficit hyperactivity disorder, short stature, dysmorphic facial features, and Wormian bones. All four novel variants are predicted to lead to a premature termination with the loss of the two conservative zinc finger motifs. This is the first report of mutations in ARID2 associated with developmental delay and ID.

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Section: Resultsmentioning

confidence: 99%

Mutations in ARID2 are associated with intellectual disabilities

Shang

Cho²,

Retterer³

et al. 2015

Neurogenetics

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“…Multiple studies have described recurrent integration into the telomerase reverse transcriptase ( TERT ) and MLL4 genes accompanied by alteration in expression (likely driven by the Enhancer 2/Core promoter region of the integrated HBV DNA) [43,66,82,83,84,88,89]. Shiraishi et al showed that TERT and CDK15 contained integration breakpoints upstream of their respective transcriptional start sites, which generated fusion transcripts that were over-expressed [90].…”

Section: Hbv Dna Integrationmentioning

confidence: 99%

HBV DNA Integration: Molecular Mechanisms and Clinical Implications

Tu¹,

Budzinska²,

Shackel³

et al. 2017

Viruses

326

302

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Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies.

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“…Recent studies reported that CDK14 is highly expressed in several malignant tumors, including HCC, taking part in the regulation of the cell cycle, tumor proliferation, migration, and invasion . Cyclin‐dependent kinase 15 was observed in an HBV–gene fusion in HCC and might participate in HBV‐driven transformation, which is an important risk factor of HCC . Expression of CDK16 is upregulated in HCC.…”

Section: Biology and Regulation Of Cdks In Hccmentioning

confidence: 99%

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

Shen

Dean²,

et al. 2019

Hepatology Research

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Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two‐thirds of HCC patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin‐dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin‐dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK‐targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.

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Integrated Analysis of Whole Genome and Transcriptome Sequencing Reveals Diverse Transcriptomic Aberrations Driven by Somatic Genomic Changes in Liver Cancers

Cited by 76 publications

References 39 publications

Mutations in ARID2 are associated with intellectual disabilities

Mutations in ARID2 are associated with intellectual disabilities

HBV DNA Integration: Molecular Mechanisms and Clinical Implications

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

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