Mutated genes, pathways and processes in tumours

Baudot, Anaı̈s; Valencia, Alfonso

doi:10.1016/j.nbt.2010.01.070

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…The classical genetic mutations, such as CIN, generally cause alternation of one or more genes, but actual variations involved in cancer are cross-over networks of cell signaling (38). Our discovery confirmed that CIN played myriad roles in tumor initiation and growth orchestrated through the complex regulation of miRNAs on their extensive target genes and the resulting impact on cell signaling.…”

Section: Discussionsupporting

confidence: 65%

Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway

Mei

Zhang

et al. 2017

Clinical Cancer Research

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Purpose: Loss of Chr9q31-33 is one of the most common chromosome imbalances of cervical cancer, but the underlying mechanism has not been well documented.Experimental Design: The loss of heterozygosity (LOH) status of Chr9q31-33 was investigated utilizing 26 microsatellite markers. We detected the expression of miR-181a2/181b2 by qRT-PCR analysis of cervical cancer cell lines and 100 paired tumor samples and corresponding adjacent non-tumor tissues. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify the prognostic value of miR-181a2/181b2. Regulation of expression was analyzed by methylation-specific PCR. The tumorsuppressing effects of miR-181a2/181b2 were determined in vitro and in vivo. The target gene and signaling pathway that mediated the function of miR-181a2/181b2 were also identified.Results: Chr9q33.3 was identified as one of the most deleted regions in cervical cancer. Underexpression of miR-181a2/ 181b2 was detected in 46% of cervical cancer and was induced by the LOH of chr9q33.3 and promoter hypermethylation. Attenuated miR-181a2/181b2 expression predicted a poor prognostic phenotype and advanced clinical stage of cervical cancer. miR-181a2/181b2 prominently dampened cell-cycle progression, suppressed cell growth, and promoted apoptosis of tumor cells in vitro. They also effectively impeded tumor formation and growth in vivo. miR-181a2/181b2 exert the tumor suppressor ability by depressing the direct target PIK3R3 (p55g) and consequently modulating the PIK3R3/Akt/FoxO signaling pathway.Conclusions: We demonstrated a cause-and-effect event beginning from loss of chr9q33.3, a frequent event in cervical cancer, to the underexpression of miR-181a2/181b2, leading to the elevated activation of the PI3K pathway.

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Section: Discussionsupporting

confidence: 65%

Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway

Mei

Zhang

et al. 2017

Clinical Cancer Research

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“…Miller dataset) and CGC there is substantial convergence of MutFam driver genes at the level of GO biological processes affected, as also shown in Baudot et al68 . Broadly, MutFams are complementary to Pfam-based methods.…”

supporting

confidence: 71%

A CATH domain functional family based approach to identify putative cancer driver genes and driver mutations

Ashford

Pang

Moya‐García

et al. 2018

Preprint

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Tumour sequencing identifies highly recurrent point mutations in cancer driver genes, but rare functional mutations are hard to distinguish from large numbers of passengers. We developed a novel computational platform applying a multi-modal approach to filter out passengers and more robustly identify putative driver genes. The primary filter identifies enrichment of cancer mutations in CATH functional families (CATH-FunFams) -structurally and functionally coherent sets of evolutionary related domains. Using structural representatives from CATH-FunFams, we subsequently seek enrichment of mutations in 3D and show that these mutation clusters have a very significant tendency to lie close to known functional sites or conserved sites predicted using CATH-FunFams. Our third filter identifies enrichment of putative driver genes in functionally coherent protein network modules confirmed by literature analysis to be cancer associated.Our approach is complementary to other domain enrichment approaches exploiting Pfam families, but benefits from more functionally coherent groupings of domains. Using a set of mutations from 22 cancers we detect 151 putative cancer drivers, of which 79 are not listed in cancer resources and include recently validated cancer genes EPHA7, DCC netrin-1 receptor and zinc-finger protein ZNF479. Table 1 Summary of protein functions and cancers for the top mutated MutFam genes having some other supporting evidence. Genes in bold were also identified in either CGC or Miller.

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“…9,10 Any errors in these processes generating aneuploidy would lead to the miscarriage, age-related infertility, and high incidence of genetic disorders such as Down syndrome in humans. [14][15][16][17] Meiotic cohesin complexes are composed of 4 essential subunits, including a meiosis-specific Smc1 subunit (Smc1b), 2 additional a-kleisins (Rad21L and Rec8) and another stromal antigen protein (Stag3). 18,19 Previous studies have investigated the functions of Smc1b in determining the axis-loop structure of synaptonemal complexes, in providing sister chromatid cohesion in metaphase I and thereafter, in protecting telomere structure, and in synapsis.…”

Section: Discussionmentioning

confidence: 99%

Smc1β is required for activation of SAC during mouse oocyte meiosis

et al. 2017

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Smc1β is a meiosis-specific cohesin subunit that is essential for sister chromatid cohesion and DNA recombination. Previous studies have shown that Smc1β-deficient mice in both sexes are sterile. Ablation of Smc1β during male meiosis leads to the blockage of spermatogenesis in pachytene stage, and ablation of Smc1β during female meiosis generates a highly error-prone oocyte although it could develop to metaphase II stage. However, the underlying mechanisms regarding how Smc1β maintains the correct meiotic progression in mouse oocytes have not been clearly defined. Here, we find that GFP-fused Smc1β is expressed and localized to the chromosomes from GV to MII stages during mouse oocyte meiotic maturation. Knockdown of Smc1β by microinjection of gene-specific morpholino causes the impaired spindle apparatus and chromosome alignment which are highly correlated with the defective kinetochore-microtubule attachments, consequently resulting in a prominently higher incidence of aneuploid eggs. In addition, the premature extrusion of polar bodies and escape of metaphase I arrest induced by low dose of nocodazole treatment in Smc1β-depleted oocytes indicates that Smc1β is essential for activation of spindle assembly checkpoint (SAC) activity. Collectively, we identify a novel function of Smc1β as a SAC participant beyond its role in chromosome cohesion during mouse oocyte meiosis.

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Mutated genes, pathways and processes in tumours

Cited by 5 publications

References 14 publications

Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway

Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway

A CATH domain functional family based approach to identify putative cancer driver genes and driver mutations

Smc1β is required for activation of SAC during mouse oocyte meiosis

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