Abstract:
:The TP53 gene is the most commonly mutated gene in human cancers and mutations in TP53 have been shown to have either gain-of-function or loss-of-function effects. Using the data generated by The Cancer Genome Atlas, we sought to define the spectrum of TP53 mutations in hepatocellular carcinomas (HCCs) and their association with clinicopathologic features, and to determine the oncogenic and mutational signatures in TP53-mutant HCCs. Compared to other cancer types, HCCs harbored distinctive mutation hotspots at V157 and R249, whereas common mutation hotspots in other cancer types, R175 and R273, were extremely rare in HCCs. In terms of clinicopathologic features, in addition to the associations with chronic viral infection and high Edmondson grade, we found that TP53 somatic mutations were less frequent in HCCs with cholestasis or tumor infiltrating lymphocytes, but were more frequent in HCCs displaying necrotic areas. An analysis of the oncogenic signatures based on the genetic alterations found in genes recurrently altered in HCCs identified four distinct TP53-mutant subsets, three of which were defined by CTNNB1 mutations, 1q amplifications or 8q24 amplifications, respectively, that co-occurred with TP53 mutations. We also found that mutational signature 12, a liver cancer-specific signature characterized by T>C substitutions, was prevalent in HCCs with wild-type TP53 or with missense TP53 mutations, but not in HCCs with deleterious TP53 mutations. Finally, whereas patients with HCCs harboring deleterious TP53 mutations had worse overall and disease-free survival than patients with TP53-wild-type HCCs, patients with HCCs harboring missense TP53 mutations did not have worse prognosis. In conclusion, our results highlight the importance to consider the genetic heterogeneity among TP53-mutant HCCs in studies of biomarkers and molecular characterization of HCCs.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Kancherla V,Abdullazade S,Matter MS,Lanzafame M,Quagliata L,Roma G,Hoshida Y,Terracciano LM,Ng CKY,Piscuoglio Sdoi
10.3389/fgene.2018.00002subject
Has Abstractpub_date
2018-02-02 00:00:00pages
2issn
1664-8021journal_volume
9pub_type
杂志文章abstract::In Colchester, Britain's oldest recorded town, during the Roman period there were areas which were clearly used solely as cemeteries. One of the most significant is at Butt Road, which includes a late Roman probable Christian cemetery with an associated building, apparently a church, that overlies and developed from a...
journal_title:Frontiers in genetics
pub_type: 杂志文章
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abstract::Fragile-X syndrome is one of the most common forms of inherited mental retardation and autistic behaviors. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Patients exhibit a variety of symptoms predominantly linked to the function of FMR...
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Frontiers in genetics
pub_type: 杂志文章
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abstract::Hexavalent chromium [Cr(VI)] is a well-known occupational carcinogen, but the mechanisms contributing to DNA damage and cell cycle alternation have not been fully characterized. To study the dose-response effects of Cr(VI) on transcription, we exposed BEAS-2B cells to Cr(VI) at concentrations of 0.2, 0.6, and 1.8 μmol...
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journal_title:Frontiers in genetics
pub_type: 杂志文章
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abstract::Primary ciliary dyskinesia (PCD), a rare genetic disorder, is mostly caused by defects in more than 40 known cilia structure-related genes. However, in approximately 20-35% of patients, it is caused by unknown genetic factors, and the inherited pathogenic factors are difficult to confirm. Kartagener syndrome (KTS) is ...
journal_title:Frontiers in genetics
pub_type: 杂志文章
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journal_title:Frontiers in genetics
pub_type: 杂志文章
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2017.00104
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abstract::Domestication to captive rearing conditions, along with targeted selective breeding have genetic consequences that vary from those in wild environments. Nile tilapia (Oreochromis niloticus) is one of the most translocated and farmed aquaculture species globally, farmed throughout Asia, North and South America, and its...
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doi:10.3389/fgene.2020.567969
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00560
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2020.00117
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abstract::Phenome-wide association studies (PheWAS) have demonstrated utility in validating genetic associations derived from traditional genetic studies as well as identifying novel genetic associations. Here we used an electronic health record (EHR)-based PheWAS to explore pleiotropy of genetic variants in the fat mass and ob...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2014.00250
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abstract::Molecular epidemiological studies have identified several risk factors linking to the genes and external factors in the pathogenesis of breast cancer. In this sense, genetic instability caused by DNA damage and DNA repair inefficiencies are important molecular events for the diagnosis and prognosis of therapies. There...
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pub_type: 杂志文章
doi:10.3389/fgene.2017.00236
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abstract::The mammalian genome is packed tightly in the nucleus of the cell. This packing is primarily facilitated by histone proteins and results in an ordered organization of the genome in chromosome territories that can be roughly divided in heterochromatic and euchromatic domains. On top of this organization several distinc...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00195
更新日期:2012-09-28 00:00:00
abstract::Seed dormancy and germination are important agronomic traits in wheat (Triticum aestivum L.) because they determine pre-harvest sprouting (PHS) resistance and thus affect grain production. These processes are regulated by Gibberellic Acid-Stimulated Regulator (GASR) genes. In this study, we identified 37 GASR genes in...
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doi:10.3389/fgene.2019.00980
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pub_type: 杂志文章
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abstract::Background: The aim of this study was to explore the Human Papillomavirus (HPV) genotype composition and intra-genotype variants within individual samples of low- and high-grade cervical cytology by deep sequencing. Clinical, cytological, sequencing, and functional/structural data were forged into an integrated varian...
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2018.00633
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pub_type: 杂志文章,评审
doi:10.3389/fgene.2019.00987
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pub_type: 杂志文章
doi:10.3389/fgene.2017.00085
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pub_type: 杂志文章,评审
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journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2012.00239
更新日期:2012-11-27 00:00:00
abstract::MicroRNAs are a class of noncoding RNAs that can be involved in the regulation of gene expression in cancers, including lung cancer. Our previous research has shown that miR-486-5p is one of the most downregulated microRNAs in tissue and serum samples of lung cancer as a good diagnostic biomarker. The objective of thi...
journal_title:Frontiers in genetics
pub_type: 杂志文章
doi:10.3389/fgene.2019.00688
更新日期:2019-07-26 00:00:00