TY - JOUR
T1 - Type 1 papillary renal cell carcinoma in a patient with schwannomatosis
T2 - Mosaic versus loss of SMARCB1 expression in respectively schwannoma and renal tumor cells
AU - Hulsebos, Theo J.M.
AU - Kenter, Susan
AU - Baas, Frank
AU - Nannenberg, Eline A.
AU - Bleeker, Fonnet E.
AU - van Minkelen, Rick
AU - van den Ouweland, Ans M.W.
AU - Wesseling, Pieter
AU - Flucke, Uta
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84958755591&partnerID=8YFLogxK
U2 - 10.1002/gcc.22338
DO - 10.1002/gcc.22338
M3 - Article
C2 - 26799435
AN - SCOPUS:84958755591
SN - 1045-2257
VL - 55
SP - 350
EP - 354
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 4
ER -