Published in:
01-09-2014 | Correspondence
SMARCA4-mutated atypical teratoid/rhabdoid tumors are associated with inherited germline alterations and poor prognosis
Authors:
Martin Hasselblatt, Inga Nagel, Florian Oyen, Kerstin Bartelheim, Robert B. Russell, Ulrich Schüller, Reimar Junckerstorff, Marc Rosenblum, Ali H. Alassiri, Sabrina Rossi, Irene Schmid, Nicholas G. Gottardo, Helen Toledano, Elisabetta Viscardi, Milagros Balbin, Leora Witkowski, Qianhao Lu, Matthew J. Betts, William D. Foulkes, Reiner Siebert, Michael C. Frühwald, Reinhard Schneppenheim
Published in:
Acta Neuropathologica
|
Issue 3/2014
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Excerpt
Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant rhabdoid brain tumors predominantly affecting young children. Biallelic inactivation of the
SMARCB1 gene (also known as hSNF5/INI1) is the characteristic underlying genetic lesion [
6]. SMARCB1 is a core member of the chromatin-remodeling complex, playing a key role in the regulation of proliferation and differentiation [
16]. Germline alterations of
SMARCB1 predisposing to the development of malignant rhabdoid tumors [Rhabdoid Tumor Predisposition Syndrome-1 (OMIM#01607)] are encountered in about one-third of children with AT/RT; the majority of
SMARCB1 germline mutations occur de novo [
3]. Some children, however, develop AT/RT without loss of SMARCB1 protein expression [
4]. We have recently demonstrated biallelic inactivation of
SMARCA4 (encoding the SMARCA4 protein also named BRG1), one of the mutually exclusive ATPase subunits of the SWI/SNF chromatin-remodeling complex, as well as transmission of
SMARCA4 germline mutations in two families [
14,
18]. Here, we show that
SMARCA4-mutated AT/RT are associated with a higher frequency of inherited germline alterations and worse prognosis as compared to SMARCB1-deficient AT/RT. …
