title: Conventional chondrosarcoma in a survivor of rhabdoid tumor: enlarging the spectrum of tumors associated with SMARCB1 germline mutations.
abstract: SMARCB1 germline mutations mainly predispose to rhabdoid tumors. However, less aggressive tumors with a later onset have also been reported in a context of SMARCB1 constitutional mutation-that is, schwannomatosis and meningiomatosis. No other tumor type has formally been observed in such a context thus far. We report on a patient treated for a thoracic malignant rhabdoid tumor at 8 years of age who subsequently developed a mandibular conventional chondrosarcoma at 13 years of age. Both tumors showed a loss of BAF47 expression. The malignant rhabdoid tumor exhibited a large 22q11.2 deletion and an intragenic deletion of SMARCB1 (exons 1 to 3), thus leading to a biallelic inactivation. A 2.8 Mbp deletion encompassing SMARCB1 was found in the germline. This context was a strong incentive to investigate SMARCB1 alterations in the second tumor. As expected, the chondrosarcoma showed the large 22q11.2 deletion but also an additional c.243C>G(p.Tyr18X) premature stop codon in the remaining allele. This report relates for the first time a pediatric conventional chondrosarcoma to the wide family of SMARCB1-deficient tumors. Moreover, we report here the first case of conventional chondrosarcoma arising in a context of constitutional SMARCB1 deletion and, thus, enlarge the spectrum of this tumor predisposition syndrome.
authors.affiliation: Département de Pathologie, Centre Hospitalier.
authors.forename: Fabien
authors.initials: F
authors.lastname: Forest
authors.forename: Audrey
authors.initials: A
authors.lastname: David
authors.forename: Sandrine
authors.initials: S
authors.lastname: Arrufat
authors.forename: Gaelle
authors.initials: G
authors.lastname: Pierron
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchere-Vince
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stephan
authors.forename: Alix
authors.initials: A
authors.lastname: Clemenson
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002648:Child; D002813:Chondrosarcoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008339:Mandibular Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016609:Neoplasms, Second Primary / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000071796:SMARCB1 Protein; D013899:Thoracic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors