title: Type 1 papillary renal cell carcinoma in a patient with schwannomatosis: Mosaic versus loss of SMARCB1 expression in respectively schwannoma and renal tumor cells.
abstract: In schwannomatosis, germline SMARCB1 or LZTR1 mutations predispose to the development of multiple benign schwannomas. Besides these, other tumors may occur in schwannomatosis patients. We present a 45-year-old male patient who developed multiple schwannomas and in addition a malignant type 1 papillary renal cell carcinoma (pRCC1). We identified a duplication of exon 7 of SMARCB1 on chromosome 22 in the constitutional DNA of the patient (c.796-2246_986 + 5250dup7686), resulting in the generation of a premature stop codon in the second exon 7 copy (p.Glu330*). The mutant SMARCB1 allele proved to be retained in three schwannomas and in the pRCC1 of the patient. Loss of heterozygosity analysis demonstrated partial loss of the wild-type SMARCB1 allele containing chromosome 22, suggesting loss of that chromosome in only a subset of tumor cells, in all four tumors. Immunohistochemical staining with a SMARCB1 antibody revealed a mosaic SMARCB1 expression pattern in the three benign schwannomas, but absence of expression in the malignant tumor cells of the pRCC1. To our knowledge, this difference in SMARCB1 protein expression has not been reported before. We conclude that a germline SMARCB1 mutation may predispose to the development of pRCC1, thereby further widening the spectrum of tumors that can develop in the context of schwannomatosis.
authors.affiliation: Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Hulsebos
authors.affiliation: Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Kenter
authors.affiliation: Department of Genome Analysis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Eline A
authors.initials: EA
authors.lastname: Nannenberg
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Fonnet E
authors.initials: FE
authors.lastname: Bleeker
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: van Minkelen
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ans M W
authors.initials: AM
authors.lastname: van den Ouweland
authors.affiliation: Department of Pathology, Nijmegen Center for Molecular Life Sciences (NCMLS), Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
authors.affiliation: Department of Pathology, Nijmegen Center for Molecular Life Sciences (NCMLS), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Uta
authors.initials: U
authors.lastname: Flucke
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D018095:Germ-Line Mutation; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000235:genetics*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors