Novel somatic alterations underlie Chinese papillary thyroid carcinoma

Yang, Chuanjia; Xu, Weixue; Ju, Gong; Liu, Zhen; Cui, Dongxu

doi:10.3233/cbm-191200

Cited by 19 publications

(23 citation statements)

References 58 publications

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“…In our verification cohort, the mutation frequencies of BRAF, TP53, MSH3, and MSH6 were 45.31% (29/64), 34.38% (22/64), 7.81% (5/64), and 12.50% (8/64), respectively, which did not fully consistent with our WES results. This is probably the reason for the different samples and other factors, but it was within the range of mutation frequency reported in the previous studies 6 , 19 . We also found that in the 23 PTCs samples, BCR, CREB3L1, and MSH6 underwent frameshift changes, a type of variation likely to affect the structure and function of these 3 gene products in the PTCs.…”

Section: Resultssupporting

confidence: 85%

“…The development and application of sequencing technologies provide new ways to identify the multitude of mutated genes and changes in expression patterns during tumorigenesis and to investigate the molecular pathogenesis of PTCs. For example, a study from Yang et al provided a list of novel candidate genes presenting somatic alterations of significant functional impact and may function as biomarkers in PTCs 6 . Smallridge RC et al compared BRAF-mutated and BRAF wild-type (BRAF-WT) tumors by RNA sequencing and identified 560 differentially expressed genes.…”

Section: Discussionmentioning

confidence: 99%

“…Although next-generation sequencing (NGS) has yielded many promising results in PTCs, the majority of the studies uncovered only well-recognized multiple PTC-related somatic mutations and signal pathways 6 - 9 . To our knowledge, NGS was rarely applied to compare the genetic backgrounds and clinical characteristics of PTCs in attempts to correlate genetic changes and clinicopathological features.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics

Rong

Feng

et al. 2021

Int. J. Med. Sci.

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The incidence of papillary thyroid carcinomas (PTCs) has increased rapidly during the past several decades. Until now, the mechanisms underlying the tumorigenesis of PTCs have remained largely unknown. Next-generation-sequencing (NGS) provides new ways to investigate the molecular pathogenesis of PTCs. To characterize the somatic alterations associated with PTCs, we performed whole-exome sequencing (WES) of PTCs from 23 Chinese patients. This study revealed somatic mutations in genes with relevant functions for tumorigenesis, such as BRAF, BCR, CREB3L2, DNMT1, IRS2, MSH6, and TP53. We also identified novel somatic gene alterations which may be potentially involved in PTC progression. Gene set enrichment analysis revealed that the cellular response to hormone stimulus, epigenetic modifications, such as protein/histone methylation and protein alkylation, as well as MAPK, PI3K-AKT, and FoxO/mTOR signaling pathways, were significantly altered in the PTCs studied here. Moreover, Protein-Protein Interaction (PPI) network analysis of our mutated gene selection highlighted EP300, KRAS, PTEN, and TP53 as major core genes. The correlation between gene mutations and clinicopathologic features of the PTCs defined by conventional ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) were assessed. These analyses established significant associations between subgroups of mutations and respectively taller-than-wide, calcified, and peak time iso- or hypo-enhanced and metastatic PTCs. In conclusion, our study supplements the genomic landscape of PTCs and identifies new actionable target candidates and clinicopathology-associated mutations. Extension of this study to larger cohorts will help define comprehensive genomic aberrations in PTCs and validate target candidates. These new targets may open methods of individualized treatments adapted to the clinicopathologic specifics of the patients.

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Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics

Rong

Feng

et al. 2021

Int. J. Med. Sci.

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“…A previous study revealed that the gene copy number of BRD9 was significantly increased in the 5p15.33 region in 12.5% (2/16) of patients with papillary thyroid carcinoma. 29 Similarly, based on single nucleotide polymorphism and fluorescence in situ hybridization analyses, Luigi Scotto et al 30 demonstrated that BRD9 protein was overexpressed in cervical cancer. In addition, studies have demonstrated that BRD9 acted as a co-factor to stabilize the structure of the SS18-SSX fusion and to maintain its oncogenic transcription in synovial sarcoma (SS).…”

Section: Introductionmentioning

confidence: 99%

Targeting BRD9 for Cancer Treatment: A New Strategy

Zhu¹,

Liao²,

Tang³

2020

OTT

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Bromodomain-containing protein 9 (BRD9) is a newly identified subunit of the non-canonical barrier-to-autointegration factor (ncBAF) complex and a member of the bromodomain family IV. Studies have confirmed that BRD9 plays an oncogenic role in multiple cancer types, by regulating tumor cell growth. The tumor biological functions of BRD9 are mainly due to epigenetic modification mediated by its bromodomain. The bromodomain recruits the ncBAF complex to the promoter to regulate gene transcription. This review summarizes the potential mechanisms of action of BRD9 in carcinogenesis and the emerging strategies for targeting BRD9 for cancer therapeutics. Although the therapeutic potential of BRD9 has been exploited to some extent, research on the detailed biological mechanisms of BRD9 is still in its infancy. Therefore, targeting BRD9 to study its biological roles will be an attractive tool for cancer diagnosis and treatment, but it remains a great challenge.

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“…IVM has also expressed several other activities, nevertheless it is originally known as inhibitor of nuclear import of host (Kosyna et al., 2015 ; van der Watt et al., 2016 ) and viral proteins, for instance simian virus SV40 large tumor antigen (T-ag) (Tay et al., 2013 ), and the nonstructural protein 5 (NS5) of Dengue virus (Wagstaff et al., 2011 ; 2012 ) . It has markedly reduce the infection of RNA Viruses like influenza (Chen, Hu, et al., 2020 ; Götz et al., 2016 ).Venezuelan equine encephalitis virus (VEEV), West Nile Virus (Yang et al., 2020 ), and DENV 1–4 (Tay et al., 2013 ). This effective broad range activity of IVM for many distinct RNA viruses is due to the fact that these all viruses depend upon IMP α / β 1 for infection and replication (Caly et al., 2012 ; Jans et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications

Qureshi

Mir

Naz

et al. 2021

Journal of Biomolecular Structure and Dynamics

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The novel corona virus (Covid-19) has become a great challenge worldwide since 2019, as no drug has been reported yet. Different clinical trials are still under way. Among them is Ivermectin (IVM), an FDA approved drug which was recently reported as a successful candidate to reduce SARS-CoV-2 viral load by inhibiting Importin- α 1 (IMP- α 1 ) protein which subsequently affects nuclear transport of viral proteins but its basic binding mode and inhibitory mechanism is unknown. Therefore, we aimed to explore the inhibitory mechanism and binding mode of IVM with IMP-α1 via different computational methods. Initially, comparative docking of IVM was performed against two different binding sites (Nuclear Localization Signal (NLS) major and minor sites) of IMP-α1 to predict the probable binding mode of IVM. Then, classical MD simulation was performed (IVM/NLS-Major site and IVM/NLS-Minor site), to predict its comparative stability dynamics and probable inhibitory mechanism. The stability dynamics and biophysical analysis of both sites highlighted the stable binding of IVM within NLS-Minor site by establishing and maintaining more hydrophobic contacts with crucial residues, required for IMP-α1 inhibition which were not observed in NLS-major site. Altogether, these results recommended the worth of IVM as a possible drug to limit the SARS-CoV-2 viral load and consequently reduces its progression. Communicated by Ramaswamy H. Sarma

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Novel somatic alterations underlie Chinese papillary thyroid carcinoma

Cited by 19 publications

References 58 publications

Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics

Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics

Targeting BRD9 for Cancer Treatment: A New Strategy

Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2: old drug with new implications

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