SMARCA4-mutated atypical teratoid/rhabdoid tumors are associated with inherited germline alterations and poor prognosis

Hasselblatt, Martin; Nagel, Inga; Oyen, Florian; Bartelheim, K.; Russell, Robert B.; Schüller, Ulrich; Junckerstorff, Reimar; Rosenblum, Marc K.; Alassiri, Ali H.; Rossi, Sabrina; Schmid, Irene; Gottardo, Nicholas G.; Toledano, Helen; Viscardi, Elisabetta; Balbı́n, Milagros; Witkowski, Leora; Lu, Qianhao; Betts, Matthew J.; Foulkes, William D.; Siebert, Reiner; Frühwald, Michael C.; Schneppenheim, Reinhard

doi:10.1007/s00401-014-1323-x

Cited by 161 publications

(129 citation statements)

References 18 publications

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“…Twenty-three of these had no sign of M+ disease in the CSF, five patients were positive (no. 4,8,14,27,30). Reasons for not applying intraventricular therapy were initiation of concomitant radiotherapy, insufficient circulation of CSF and/or CNS infections.…”

Section: Response To Chemotherapymentioning

confidence: 99%

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Improved 6‐year overall survival in AT/RT – results of the registry study Rhabdoid 2007

et al. 2016

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Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatmentrelated death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality Cancer MedicineOpen Access 1766

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Section: Response To Chemotherapymentioning

confidence: 99%

“…The majority of rhabdoid tumors demonstrate mutations in SMARCB1 (INI1, hSNF5) [2,3] and rarely SMARCA4 (BRG1) [4]. Survival remains unsatisfactory due to the aggressive nature of the disease and ranges from 15% to 40% even with intensive multimodality therapy [5,6].…”

Section: Introductionmentioning

confidence: 99%

Improved 6‐year overall survival in AT/RT – results of the registry study Rhabdoid 2007

et al. 2016

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“…The mutations occur predominantly in SMARCB1, but recent studies have reported a second disease loci SMARCA4. The clinical significance has yet to be determined, but mutations in SMARCA4 have been associated with worse prognosis compared to SMARCB1 [59].…”

Section: Geneticsmentioning

confidence: 99%

Recent developments in brain tumor predisposing syndromes

2015

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“…Female carriers of truncating mutations are at risk for SCCOHT, and infant carriers of both genders may be at risk for rhabdoid tumours (table 1). As SMARCA4 -mutated rhabdoid tumours have not been reported in patients older than 46 months, the development of these tumours in older carriers is unlikely 100. However, the oldest woman to date diagnosed definitively with SCCOHT (showing loss of SMARCA4 staining in her tumour) was 56 years old at diagnosis 90.…”

Section: Small Cell Carcinoma Of the Ovary Of Hypercalcaemic Typementioning

confidence: 98%

Paediatric ovarian tumours and their associated cancer susceptibility syndromes

et al. 2017

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Non-epithelial ovarian tumours are rare neoplasms that occasionally arise in childhood and adolescence. They can be associated with various cancer susceptibility syndromes. The morphological overlap seen across these tumours and their rarity can make the diagnosis challenging. In the case of an incorrect diagnosis, the underlying genetic susceptibility may be missed. In this review, we outline the genetic background of ovarian non-epithelial tumours arising in children, emphasizing the genes harbouring pathogenic germline variants associated with each tumour type. Specifically, juvenile granulosa cell tumours, Sertoli-Leydig cell tumours, sex cord tumours with annular tubules, Sertoli cell tumours, germ cell tumours and small cell carcinoma of the ovary of hypercalcaemic type are discussed in this review. For each tumour type, we detail the personal and family history features and the presenting characteristics of the ovarian tumour as well as the pathological features and molecular markers that point towards a cancer predisposition syndrome. Throughout, we stress the need for specialised pathological review in difficult cases.

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SMARCA4-mutated atypical teratoid/rhabdoid tumors are associated with inherited germline alterations and poor prognosis

Cited by 161 publications

References 18 publications

Improved 6‐year overall survival in AT/RT – results of the registry study Rhabdoid 2007

Improved 6‐year overall survival in AT/RT – results of the registry study Rhabdoid 2007

Recent developments in brain tumor predisposing syndromes

Paediatric ovarian tumours and their associated cancer susceptibility syndromes

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