Specific-site methylation of tumour suppressor ANKRD11 in breast cancer

Lim, Sue Ping; Wong, Nicholas C.; Suetani, Rachel J.; Ho, Kristen; Ng, Jane; Neilsen, Paul M.; Gill, P. Grantley; Kumar, Raman; Callen, David F.

doi:10.1016/j.ejca.2012.03.023

Cited by 29 publications

(17 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ANKRD11 can also suppress the oncogenic potential of P53 Gain‐Of‐Function mutant . ANKRD11 expression was found lower in breast tumor tissues and breast cancer cell lines when compared to normal breast tissues or nonmalignant immortalized breast epithelial cells . Restoring ANKRD11 expression in breast cancer cell lines can suppress tumor cell growth in the presence of P53 that can bind DNA .…”

Section: Discussioncontrasting

confidence: 50%

Whole‐exome sequencing of ovarian cancer families uncovers putative predisposition genes

Zhu

Zhang

Chen

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Despite the identification of several ovarian cancer (OC) predisposition genes, a large proportion of familial OC risk remains unexplained. We adopted a two‐stage design to identify new OC predisposition genes. We first carried out a large germline whole‐exome sequencing study on 158 patients from 140 families with significant OC history, but without evidence of genetic predisposition due to BRCA1/2. We then evaluated the potential candidate genes in a large case–control association study involving 381 OC cases in the Cancer Genome Atlas project and 27,173 population controls from the Exome Aggregation Consortium. Two new putative OC risk genes were identified, namely, ANKRD11, a putative tumor suppressor, and POLE, an enzyme involved in DNA repair and replication. These two genes likely confer moderate OC risk. We performed in vitro experiments and showed an ANKRD11 mutation identified in our patients markedly lowered the protein expression by compromising protein stability. Upon future validation and functional characterization, these genes may shed light on cancer etiology along with improving ascertainment power and preventive care of individuals at high risk of OC.

show abstract

Section: Discussioncontrasting

confidence: 50%

Whole‐exome sequencing of ovarian cancer families uncovers putative predisposition genes

Zhu

Zhang

Chen

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Two patients showed hematological abnormalities (one had a pancytopenia with bone marrow hypoplasia and the second had anemia and leukopenia). Only 1 patient was previously reported with acute myeloid leukemia [Goldenberg et al, 2016], and a role of ANKRD11 in cancer predisposition was proposed, but not confirmed [Neilsen et al, 2008;Lim et al, 2012]. The presence of thrombocytopenia was pointed out as a possible feature distinguishing between KBG syndrome and 16q24 microdeletion syndrome, where ANKRD11 flanking genes are also involved [Novara et al, 2017].…”

Section: Discussionmentioning

confidence: 99%

Novel Mutations and Unreported Clinical Features in KBG Syndrome

Scarano¹,

Tassone²,

Graziano

et al. 2019

Mol Syndromol

View full text Add to dashboard Cite

KBG syndrome is an autosomal dominant disorder caused by pathogenic variants within ANKRD11 or deletions of 16q24.3 which include ANKRD11. It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. We report 12 unrelated patients where a clinical diagnosis of KBG was suspected and confirmed by targeted analyses. Nine patients showed a point mutation in ANKRD11 (none of which were previously reported) and 3 carried a 16q24.3 deletion. All patients presented with typical facial features and macrodontia. Skeletal abnormalities were constant, and the majority of patients showed joint stiffness. Three patients required growth hormone treatment with a significant increase of height velocity. Brain malformations were identified in 8 patients. All patients showed behavioral abnormalities and most had developmental delay. Two patients had hematological abnormalities. We emphasize that genetic analysis of ANKRD11 can easily reach a detection rate higher than 50% thanks to clinical phenotyping, although it is known that a subset of ANKRD11-mutated patients show very mild features and will be more easily identified through the implementation of gene panels or exome sequencing. Joint stiffness was reported previously in few patients, but it seems to be a common feature and can be helpful for the diagnosis. Hematological abnormalities could be present and warrant a specific follow-up.

show abstract

“…Briefly, we preliminary searched the highly conserved region ~2 kb upstream in the promoter regions of lncRNAs and found the promoter sequences of lncRNAs in an online databases (Ensembl: http://asia.ensembl.org/index.html). 58, 59, 60, 61, 62 Then, the JASPAR (http://jaspar.genereg.net/), 63 TRAP (http://trap.molgen.mpg.de/cgi-bin/trap_two_seq_form.cgi), 64 rVista (http://www.rcista.dcode.org) 65 and TFSEARCH (http://www.cbrc.jp/research/db/TFSEARCH.html) 66 results revealed that there were NF- κ B-binding sites in Gm4419 promoter region. Meanwhile, using the same approach above, the sites of NF- κ B binding to the NLRP3 inflammasome promoter were detected.…”

Section: Methodsmentioning

confidence: 99%

LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy

et al. 2017

View full text Add to dashboard Cite

Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. Recent researches have shown the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome are associated with inflammation in the progression of DN, but the exact mechanism is unclear. Long noncoding RNAs (lncRNAs) have roles in the development of many diseases including DN. However, the relationship between lncRNAs and inflammation in DN remains largely unknown. Our previous study has revealed that 14 lncRNAs are abnormally expressed in DN by RNA sequencing and real-time quantitative PCR (qRT-PCR) in the renal tissues of db/db DN mice. In this study, these lncRNAs were verified their expressions by qRT-PCR in mesangial cells (MCs) cultured under high- and low-glucose conditions. Twelve lncRNAs displayed the same expressional tendencies in both renal tissues and MCs. In particular, long intergenic noncoding RNA (lincRNA)-Gm4419 was the only one associating with NF-κB among these 12 lncRNAs by bioinformatics methods. Moreover, Gm4419 knockdown could obviously inhibit the expressions of pro-inflammatory cytokines and renal fibrosis biomarkers, and reduce cell proliferation in MCs under high-glucose condition, whereas overexpression of Gm4419 could increase the inflammation, fibrosis and cell proliferation in MCs under low-glucose condition. Interestingly, our results showed that Gm4419 could activate the NF-κB pathway by directly interacting with p50, the subunit of NF-κB. In addition, we found that p50 could interact with NLRP3 inflammasome in MCs. In conclusion, our findings suggest lincRNA-Gm4419 may participate in the inflammation, fibrosis and proliferation in MCs under high-glucose condition through NF-κB/NLRP3 inflammasome signaling pathway, and may provide new insights into the regulation of Gm4419 during the progression of DN.

show abstract

Specific-site methylation of tumour suppressor ANKRD11 in breast cancer

Cited by 29 publications

References 18 publications

Whole‐exome sequencing of ovarian cancer families uncovers putative predisposition genes

Whole‐exome sequencing of ovarian cancer families uncovers putative predisposition genes

Novel Mutations and Unreported Clinical Features in KBG Syndrome

LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy

Contact Info

Product

Resources

About