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Novel germ‐line deletion of SNF5/INI1/SMARCB1 gene in neonate presenting with congenital malignant rhabdoid tumor of kidney and brain primitive neuroectodermal tumor
Author(s) -
Kusafuka Takeshi,
Miao Jiangyong,
Yoneda Akihiro,
Kuroda Seika,
Fukuzawa Masahiro
Publication year - 2004
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20026
Subject(s) - smarcb1 , biology , exon , loss of heterozygosity , primitive neuroectodermal tumor , single strand conformation polymorphism , wilms' tumor , microbiology and biotechnology , gene , germline , allele , cancer research , genetics , gene expression , chromatin remodeling , chemotherapy
Abstract We describe a neonate who had a rare tumor combination of a malignant rhabdoid tumor of the kidney (MRTK) and a brain primitive neuroectodermal tumor (PNET). Genetic alterations of the SNF5/INI1/SMARCB1 gene were investigated by PCR–single‐strand conformation polymorphism (SSCP), loss of heterozygosity (LOH), sequence, and karyotyping analyses, and the gene expression level was determined by real‐time quantitative RT‐PCR analysis. PCR band signals of each exon of the hSNF5/INI1 were weak or nearly undetectable in both MRTK and PNET, whereas those of the corresponding normal kidney were clearly detected. Aberrantly migrating SSCP bands led to identification of a nucleotide change in intron 8. Although this was regarded as a polymorphism, only the changed nucleotide was observed in the normal kidney of the patient. Allelic states in the parents were heterozygous for the polymorphism in the father and homozygous for the normal sequence in the mother. Thus, it was evident that a substantial genetic part of the maternal normal allele including SNF5/INI1 was deleted as a de novo germ‐line mutation. In both tumors, LOH at microsatellite loci on the long arm of chromosome 22 was evident, and expression of SNF5/INI1 mRNA was drastically decreased compared to that in control tissues (0.7–3.9 vs. 123.6–153.5). Deletion of a substantial genetic part demonstrated in our patient is the novel appearance of a germ‐line deletion of the SNF5/INI1 gene. Additional large somatic deletions resulted in total inactivation of the gene in both tumors. Our patient provides evidence for an important role of SNF5/INI1 germ‐line mutation in predisposing patients to multiple rhabdoid tumors. © 2004 Wiley‐Liss, Inc.