Genetic similarities have been found within<unk>  tumors. In particular, the chromosomal 22 deletion is very common in<unk> s. The chromosome 22 area contains the hSNF5/INI1 gene that appears to function as a classic tumor suppressor gene. Most<unk>  tumors have INI1 deletions whether they occur in the CNS, kidney, or elsewhere. This mutation is viewed as the "first hit" which predisposes children to malignancies. INI1/hSNF5, a component of the chromatin remodeling SWI/SNF complex, is a critical tumor suppressor biallelically inactivated in<unk>  tumors. Identification of INI1 as a tumor suppressor has facilitated accurate diagnosis of<unk>  tumors. The rate of transcription for SWI/SNF and HDAC complexes seem to be regulated by the INI1 gene. The SWI/SNF complex plays a role in chromatin remodeling.<unk>  is the first pediatric brain tumor for which a candidate tumor suppressor gene has been identified. A mutation or deletion in the INI1/hSNF5 gene occurs in the majority of<unk>  tumors. Up to 90% of<unk>  cases involve chromosome 22 deletion. This is mainly point mutations in the hSNF5/INI1 gene (i.e., one can diagnosis<unk>  without a chromosome 22 deletion elsewhere). The hSNF5/INI1 gene regulates 15 or so proteins in the chromatin structure. In addition, the OPN gene has a higher expression in<unk>  tumors. All of the<unk>  cancers are believed to be not associated with the hSNF5/INI1 gene, as 14 additional proteins in the chromatin structure are controlled by other genes. There are also some emerging mouse models of the<unk>  cancer as well as experimental cell lines derived from tumors. Despite these advances, the function of the gene is not yet understood. There is not enough known about the function of INI1, either as an independent modulator of gene expression or through its association with the SWI/SNF complex, to be able to use specific targeted biological agents for treatment. Prospective clinical and biologic trials are greatly needed to understand the efficacy of therapeutic interventions, as well as the role of the gene. Risk for siblings and other members of the family<unk> s are very rare, and absolute risk to siblings is not reported in the literature. However, some reports exist of<unk> s presenting in two members of the same family, or one family member with an<unk>  and another with a renal<unk>  tumor or other CNS tumor. These are suspected to arise from germline genetic mutations in a parent shared by affected siblings. * A three-generation family is known in which two half-brothers were diagnosed with CNS<unk> s <unk> . The two boys, diagnosed at 2 months and 17 months of age, had a germline insertion mutation in exon 4 of the INI1 gene that was inherited from their healthy mother. A maternal uncle died in childhood from a brain tumor and a malignant<unk>  tumor of the kidney. The identification of two unaffected carriers in a family segregating a germline mutation and<unk>  tumor supports the hypothesis that variable risks of development of<unk>  tumor in the context of a germline mutation may exist. Most<unk>  tumors may occur in a developmental window. This family highlights the importance of mutation analysis in all patients with a suspected<unk>  tumor. * In the first case report of monozygotic twins, both with brain tumors having similar genetic alterations, authors suggest a common genetic pathway. * A case was reported of an infant who developed both<unk>  and renal<unk>  tumors that were identical in gross and immunologic histology. * A family has had multiple generations of posterior fossa tumors including<unk>  tumors and choroid plexus carcinoma. A germline mutation (SMARCB1) was found in both affected and some unaffected family members. * Two sisters were diagnosed with<unk> s 15 days apart. A case report stated no karyotypic anomalies were noted. * Three siblings had a mutation of the SMARCB1 gene and one had a choroid plexus carcinoma and two had an<unk> . Although the mother had a normal somatic DNA, the mutation apparently was inherited from the mother's germline due to a mutation during oogenesis. * Izycka-Swieszewska et al. describe a five-month-old child with an<unk> , whose father was diagnosed with a primitive neuroectodermal tumor (PNET) of the spinal canal. Fluorescent in situ hybridization analysis showed significant genetic differences in the specimens which suggest that the occurrence of these virulent CNS malignancies within a single family was coincidental.
Atypical teratoid rhabdoid tumor
Malignant rhabdoid tumour
Pediatric ependymoma
Neurothekeoma
Endodermal sinus tumor
Sialoblastoma
Ameloblastoma
Primitive neuroectodermal tumor