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Molecular Basis of Beckwith-Wiedemann Syndrome Spectrum with Associated Tumors and Consequences for Clinical Practice.

ABSTRACT: Beckwith-Wiedemann syndrome (BWS, OMIM 130650) is a congenital imprinting condition with a heterogenous clinical presentation of overgrowth and an increased childhood cancer risk (mainly nephroblastoma, hepatoblastoma or neuroblastoma). Due to the varying clinical presentation encompassing classical, clinical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly, the syndromic entity was extended to the Beckwith-Wiedemann spectrum (BWSp). The tumor risk of up to 30% depends on the molecular subtype of BWSp with causative genetic or epigenetic alterations in the chromosomal region 11p15.5. The molecular diagnosis of BWSp can be challenging for several reasons, including the range of causative molecular mechanisms which are frequently mosaic. The molecular basis of tumor formation appears to relate to stalled cellular differentiation in certain organs that predisposes persisting embryonic cells to accumulate additional molecular defects, which then results in a range of embryonal tumors. The molecular subtype of BWSp not only influences the overall risk of neoplasia, but also the likelihood of specific embryonal tumors.

SUBMITTER: Eggermann T

PROVIDER: S-EPMC9265096 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Molecular Basis of Beckwith-Wiedemann Syndrome Spectrum with Associated Tumors and Consequences for Clinical Practice.

Eggermann Thomas T Maher Eamonn R ER Kratz Christian P CP Prawitt Dirk D

Cancers 20220623 13

Beckwith-Wiedemann syndrome (BWS, OMIM 130650) is a congenital imprinting condition with a heterogenous clinical presentation of overgrowth and an increased childhood cancer risk (mainly nephroblastoma, hepatoblastoma or neuroblastoma). Due to the varying clinical presentation encompassing classical, clinical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly, the syndromic entity was extended to the Beckwith-Wiedemann spectrum (BWSp). The tumor risk o ...[more]

PMID: 35804856

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Project description:Epigenetics has achieved a profound impact in the biomedical field, providing new experimental opportunities and innovative therapeutic strategies to face a plethora of diseases. In the rare diseases scenario, Beckwith-Wiedemann syndrome (BWS) is a pediatric pathological condition characterized by a complex molecular basis, showing alterations in the expression of different growth-regulating genes. The molecular origin of BWS is associated with impairments in the genomic imprinting of two domains at the 11p15.5 chromosomal region. The first domain contains three different regions: insulin growth like factor gene (IGF2), H19, and abnormally methylated DMR1 region. The second domain consists of cell proliferation and regulating-genes such as CDKN1C gene encoding for cyclin kinase inhibitor its role is to block cell proliferation. Although most cases are sporadic, about 5-10% of BWS patients have inheritance characteristics. In the 11p15.5 region, some of the patients have maternal chromosomal rearrangements while others have Uniparental Paternal Disomy UPD(11)pat. Defects in DNA methylation cause alteration of genes and the genomic structure equilibrium leading uncontrolled cell proliferation, which is a typical tumorigenesis event. Indeed, in BWS patients an increased childhood tumor predisposition is observed. Here, we summarize the latest knowledge on BWS and focus on the impact of epigenetic alterations to an increased cancer risk development and to metabolic disorders. Moreover, we highlight the correlation between assisted reproductive technologies and this rare disease. We also discuss intriguing aspects of BWS in twinning. Epigenetic therapies in clinical trials have already demonstrated effectiveness in oncological and non-oncological diseases. In this review, we propose a potential "epigenetic-based" approaches may unveil new therapeutic options for BWS patients. Although the complexity of the syndrome is high, patients can be able to lead a normal life but tumor predispositions might impair life expectancy. In this sense epigenetic therapies should have a supporting role in order to guarantee a good prognosis.

Dataset Information

Molecular Basis of Beckwith-Wiedemann Syndrome Spectrum with Associated Tumors and Consequences for Clinical Practice.

Publications

Molecular Basis of Beckwith-Wiedemann Syndrome Spectrum with Associated Tumors and Consequences for Clinical Practice.

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