Long-term survival and transmission of INI1-mutation via nonpenetrant males in a family with rhabdoid tumour predisposition syndrome
| Autor: | J. L. J. M. Teepen, Cees C. Tijssen, M P W A Houben, A. C. J. Ammerlaan, Theo J. M. Hulsebos, Pieter Wesseling, A Ararou, Frank Baas |
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| Přispěvatelé: | ANS - Amsterdam Neuroscience, Neurology, Genome Analysis, CCA -Cancer Center Amsterdam |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cancer Research Time Factors INI1 Adolescent Myoepithelioma Chromosomal Proteins Non-Histone Chromosomes Human Pair 22 DNA Mutational Analysis Inheritance Patterns Penetrance Biology paediatric brain tumour Germline Rhabdoid Tumor Predisposition Syndrome Exon Germline mutation Genotype-phenotype distinction Translational research [ONCOL 3] Humans Family Genetic Predisposition to Disease Germ-Line Mutation Rhabdoid Tumor Molecular diagnosis prognosis and monitoring [UMCN 1.2] Genetics Sex Characteristics Base Sequence Infant Genetics and Genomics SMARCB1 Protein Syndrome Tissue engineering and pathology [NCMLS 3] Survival Analysis Pedigree DNA-Binding Proteins Tumor microenvironment [UMCN 1.3] rhabdoid tumour predisposition syndrome germline mutation Oncology Child Preschool Mutation testing Cancer research Female Microsatellite Repeats Transcription Factors Immunity infection and tissue repair [NCMLS 1] |
| Zdroj: | British journal of cancer, 98(2), 474-479. Nature Publishing Group British Journal of Cancer, 98, 2, pp. 474-9 British Journal of Cancer, 98, 474-9 British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Item does not contain fulltext Rhabdoid tumour predisposition syndrome (RTPS) is a rare syndrome caused by inheritance of a mutated INI1 gene for which only two multigeneration families have been reported. To further characterise the genotype and phenotype of RTPS, we present a third family in which at least three cousins developed an atypical teratoid/rhabdoid tumour (AT/RT) at a young age. Two of these patients showed unusual long survival, and one of these developed an intracranial meningioma and a myoepithelioma of the lip in adulthood. Mutation analysis of INI1 revealed a germline G>A mutation in the donor splice site of exon 4 (c.500+1G>A) in the patients and in their unaffected fathers. This mutation prevents normal splicing and concomitantly generates a stop codon, resulting in nonsense-mediated mRNA decay. Biallelic inactivation of INI1 in the tumours, except for the meningioma, was confirmed by absence of nuclear INI1-protein staining. The myoepithelioma of one of the patients carried an identical somatic rearrangement in the NF2 gene as the AT/RT, indicating that both tumours originated from a common precursor cell. In conclusion, this study demonstrates for the first time transmission of a germline INI1-mutation in a RTPS family via nonpenetrant males, long-term survival of two members of this family with an AT/RT, and involvement of INI1 in the pathogenesis of myoepithelioma. |
| Databáze: | OpenAIRE |
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