Adrenocortical carcinoma in atypical Beckwith‐Wiedemann syndrome due to loss of methylation at imprinting control region 2

Eltan, Mehmet; Ateş, Esra Arslan; Cerit, Kıvılcım Karadeniz; Menevşe, Tuba Seven; Kaygusuz, Sare Betül; Eker, Nurşah; Bağcı, Pelin; Ergelen, Rabia; Turan, Serap; Bereket, Abdullah; Güran, Tülay

doi:10.1002/pbc.28042

Cited by 8 publications

(9 citation statements)

References 10 publications

(15 reference statements)

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“…They were found in Li-Fraumeni syndrome [87,93,94], multiple endocrine neoplasia type 1 [95], neurofibromatosis type 1 [96] and familial adenomatous polyposis [97]. In addition, paediatric ACCs were found in Beckwith-Wiedemann syndrome [98,99].…”

Section: Clinical Featuresmentioning

confidence: 99%

Adrenocortical Carcinoma: Updates of Clinical and Pathological Features after Renewed World Health Organisation Classification and Pathology Staging

Lam

2021

Biomedicines

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Adrenocortical carcinoma (ACC) is a heterogenous group of diseases with different clinical behaviour between adult and paediatric patients. In addition, three histological variants, oncocytic, myxoid and sarcomatoid are noted on the recent World Health Organisation (WHO) classification of ACC. A review of recent literature showed that the different types of ACC have distinctive demographic data, clinical presentation, pathology, biological behaviour, genomic and patients’ prognosis. In addition, recent updates of pathology staging for ACC allow refinement of prognostic grouping for planning treatment of the patients with ACC. These advances in genomic, pathology and staging have driven the development of standardisation of pathology reporting. International standardisation of pathological reporting of adrenocortical carcinoma and adaption to local pathology communities provide universal platforms for clinicians and researchers involved in the management of patients with ACC. To conclude, all these advances in the field of pathology will improve development of management strategies including improvement of clinical care, development of prognostic markers and testing of novel therapeutic approaches for patients with adrenocortical carcinoma.

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Section: Clinical Featuresmentioning

confidence: 99%

Adrenocortical Carcinoma: Updates of Clinical and Pathological Features after Renewed World Health Organisation Classification and Pathology Staging

Lam

2021

Biomedicines

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“… 7 The most common cancers associated with BWSp are nephroblastoma and hepatoblastoma. 4 More rare cancers described in children with BWSp include acute lymphoblastic leukaemia, 8 , 9 adrenocortical carcinoma, 10 hemangiotheloma, 11 melanoma, 9 , 12 neuroblastoma and ganglioneuroblastoma, 9 pancreatoblastoma, 13 phaeochromocytoma, 14 rhabdomyosarcoma 15 and thyroid cancer. 16 The published overall childhood cancer risk in the various subgroups are the following: IC2-LOM 2.6%, IC1-GOM 28.1% (mainly Wilms tumour), UPDpat 16% (mainly Wilms tumour and hepatoblastoma), CDKN1C pathogenic variant 6.9% (mainly neuroblastoma) (reviewed in 1 ).…”

Section: Introductionmentioning

confidence: 99%

Cancer incidence and spectrum among children with genetically confirmed Beckwith-Wiedemann spectrum in Germany: a retrospective cohort study

et al. 2020

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Background Beckwith-Wiedemann syndrome (BWS) is a cancer predisposition syndrome caused by defects on chromosome 11p15.5. The quantitative cancer risks in BWS patients depend on the underlying (epi)genotype but have not yet been assessed in a population-based manner. Methods We identified a group of 321 individuals with a molecularly confirmed diagnosis of BWS and analysed the cancer incidence up to age 15 years and cancer spectrum by matching their data with the German Childhood Cancer Registry. Results We observed 13 cases of cancer in the entire BWS cohort vs 0.4 expected. This corresponds to a 33-fold increased risk (standardised incidence ratio (SIR) = 32.6; 95% confidence interval = 17.3-55.7). The specific cancers included hepatoblastoma (n = 6); nephroblastoma (n = 4); astrocytoma (n = 1); neuroblastoma (n = 1) and adrenocortical carcinoma (n = 1). The cancer SIR was highest in patients with a paternal uniparental disomy of 11p15.5 (UPDpat). A high cancer risk remained when cases of cancer diagnosed prior to the BWS diagnosis were excluded. Conclusions This study confirms an increased cancer risk in children with BWS. Our findings suggest that the highest cancer risk is associated with UPDpat. We were unable to confirm an excessive cancer risk in patients with IC1 gain of methylation (IC1-GOM) and this finding requires further investigation.

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“…Remarkably, four of the patients with germline paternal 11p15 UPD (cases #3,4,5,6), and three previously reported cases of ACT with hypomethylation at ICR2 (24,25) did not have clinical manifestations of BWS. These findings suggest that chromosome 11p15 abnormalities are associated with diverse phenotypes ranging from cases that fulfil the entire criteria of classic BWS to those with embryonal tumors-only.…”

Section: Discussionmentioning

confidence: 77%

Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment

et al. 2021

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Pediatric adrenocortical tumors (ACTs) are rare and heterogeneous. Approximately 50% of children with ACT carry a germline TP53 variant; however, the genetic underpinning of remaining cases has not been elucidated. In patients having germline TP53 variants, loss of maternal chromosome 11 and duplication of the paternal copy [paternal uniparental disomy, (UPD)] occurs early in tumorigenesis and explains the overexpression of IGF2, the hallmark of pediatric ACT. Beckwith-Wiedemann syndrome (BWS) is also associated with overexpression of IGF2 due to disruption of the 11p15 loci, including segmental UPD. Here, we report six children with ACT with wild type TP53 and germline paternal 11p15 UPD. Median age of five girls and one boy was 3.2 years (range 0.5-11 years). Two patients met the criteria for BWS before diagnosis of ACT. However, ACT was the first and only manifestation of paternal 11p15 UPD in four children. Tumor weight ranged from 21.5 g to 550 g. Despite poor prognostic features at presentation, such as pulmonary metastasis, bilateral adrenal involvement, and large tumors, all patients are alive 8-21 years after cancer diagnosis. Our observations suggest that children with ACT and wild type TP53, irrespective of their age, should be screened for germline abnormalities in chromosome 11p15.

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Adrenocortical carcinoma in atypical Beckwith‐Wiedemann syndrome due to loss of methylation at imprinting control region 2

Cited by 8 publications

References 10 publications

Adrenocortical Carcinoma: Updates of Clinical and Pathological Features after Renewed World Health Organisation Classification and Pathology Staging

Adrenocortical Carcinoma: Updates of Clinical and Pathological Features after Renewed World Health Organisation Classification and Pathology Staging

Cancer incidence and spectrum among children with genetically confirmed Beckwith-Wiedemann spectrum in Germany: a retrospective cohort study

Adrenocortical Tumors in Children With Constitutive Chromosome 11p15 Paternal Uniparental Disomy: Implications for Diagnosis and Treatment

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