Research Papers:

Embryonic signature distinguishes pediatric and adult rhabdoid tumors from other SMARCB1-deficient cancers

Wilfrid Richer, Julien Masliah-Planchon, Nathalie Clement, Irene Jimenez, Laetitia Maillot, David Gentien, Benoît Albaud, Walid Chemlali, Christine Galant, Frederique Larousserie, Pascaline Boudou-Rouquette, Amaury Leruste, Celine Chauvin, Zhi Yan Han, Jean-Michel Coindre, Pascale Varlet, Paul Freneaux, Dominique Ranchère-Vince, Olivier Delattre and Franck Bourdeaut _

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Oncotarget. 2017; 8:34245-34257. https://doi.org/10.18632/oncotarget.15939

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Wilfrid Richer1,*, Julien Masliah-Planchon2,*, Nathalie Clement1, Irene Jimenez1,3, Laetitia Maillot2, David Gentien4, Benoît Albaud4, Walid Chemlali2, Christine Galant5, Frederique Larousserie6, Pascaline Boudou-Rouquette7, Amaury Leruste1, Celine Chauvin1, Zhi Yan Han1, Jean-Michel Coindre8, Pascale Varlet9, Paul Freneaux10, Dominique Ranchère-Vince11, Olivier Delattre1,2, Franck Bourdeaut1,3

1Paris-Sciences-Lettres, Institut Curie Research Center, INSERMU830 and SiRIC, Laboratory of Translational Research in Pediatric Oncology, Paris, France

2Paris-Sciences-Lettres, Institut Curie Hospital, Laboratory of Somatic Genetics, Paris, France

3Paris-Sciences-Lettres, Institut Curie Hospital, Department of Pediatric Oncology-Adolescents and Young Adults, Paris, France

4Paris-Sciences-Lettres, Institut Curie Research Center, Department of Translational Research, Genomic Platform, Paris, France

5University Hospital of Leuven, Department of Pathology, Leuven, Belgium

6Cochin University Hospital, Universite Rene Descartes, Sorbonne Paris Cite, Assistance Publique Hôpitaux de Paris, Department of Pathology, Paris, France

7Cochin University Hospital, Assistance Publique Hôpitaux de Paris, Department of Oncology, Paris, France

8Institut Bergognie, Department of Pathology, Bordeaux, France

9University Sainte-Anne Hospital, Paris, France

10Paris-Sciences-Lettres, Institut Curie Hospital, Department of Pathology, Paris, France

11Centre Leon Berard, Department of Pathology, Lyon, France

*These authors contributed equally to this work

Correspondence to:

Franck Bourdeaut, email: [email protected]

Keywords: rhabdoid, SMARCB1, TET1, DNMT3B, adult

Received: November 25, 2016     Accepted: February 22, 2017     Published: March 06, 2017


Extra-cranial rhabdoid tumors (RT) are highly aggressive malignancies of infancy, characterized by undifferentiated histological features and loss of SMARCB1 expression. The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC). Moreover, late cases occurring in adults are now increasingly reported, raising the question of differential diagnoses and emphasizing nosological issues. To address this issue, we have analyzed the expression profiles of a training set of 32 SMARCB1-deficient tumors (SDT), with ascertained diagnosis of RT (n = 16, all < 5 years of age), ES (n = 8, all > 10 years of age), UC (n = 3) and RMC (n = 5). As compared with other SDT, RT are characterized by an embryonic signature, and up-regulation of key-actors of de novo DNA methylation processes. Using this signature, we then analysed the expression profiling of 37 SDT to infer the appropriate diagnosis. Thirteen adult onset tumors showed strong similarity with pediatric RT, in spite of older age; by exome sequencing, these tumors also showed genomic features indistinguishable from pediatric RT. In contrary, 8 tumors were reclassified within carcinoma, ES or UC categories, while the remaining could not be related to any of those entities. Our results demonstrate that embryonic signature is shared by all RT, whatever the age at diagnosis; they also illustrate that many adult-onset SDT of ambiguous histological diagnosis are clearly different from RT. Finally, our study paves the way for the routine use of expression-based signatures to give accurate diagnosis of SDT.

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