Malignant Rhabdoid Tumor of the Liver, p53, hSNF5/INI1 genes and Apoptosis

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Figures:
1: CT abdomen post contrast. There is a large heterogenous mass in left lobe and anterior right lobe of the liver. 2: 3D volume rendered CT image of mass. 3: Post gadolinium MRI. The mass shows intense enhancement with areas of nonenhancing necrosis. 4: T2 MRI. The mass shows increased T2 signal intensity. The mass was confined within the liver.

Malignant rhabdoid tumors occur during early childhood in the kidneys, soft tissues, and the central nervous system among other sites. Hepatic malignant rhabdoid tumor is rare but has been described. Prognosis is poor because of the rapid growth rate, early metastases and marked resistance to current radio- and chemo-therapy .The most common sites of metastasis are the lymph nodes and the lungs. Intracranial metastases have been described. Radiographically they are large heterogeneous tumors on CT and MRI at the time of presentation. They demonstrate contrast enhancement and areas of necrosis. They can be locally invasive.

Malignant rhabdoid tumors show alterations of the hSNF5/INI1 gene. This gene codes for a member of the SWI/SNF protein complexes involved chromatin-remodeling that activates or represses transcription of target genes. SWI/SNF activity is required for transcriptional repression and inhibition of cell proliferation. hSNF5/INI1 protein co-operates with several other important cellular factors such as c-Myc. Overexpression of c-Myc, a nuclear phosphoprotein that regulates DNA replication and cell division, is consistently seen in rhabdoid cells. High levels and unusual distribution of p53 protein have been observed in rhabdoid cells, but p53 gene expression does not seem to be increased.

Experiments have shown that when hSNF5/INI1 protein is re-introduced into rhabdoid cells, it prevents cell proliferation. hSNF5/INI1 overexpression appears to induce apoptosis in rhabdoid cell lines. Perturbations of the p53 pathway and a reduced apoptotic response in rhabdoid tumor cells might contribute to the resistance of malignant rhabdoid tumors to antineoplastic treatments. The Ras/PI3-K/AKT signaling pathway seems to be involved in the dysfunctions induced in these cells by the mutation in the hSNF5/INI1 gene and probably results in increased malignant cell survival factors.

Reference:
Apoptotic response of malignant rhabdoid tumor cellsSilvano Nocentini1
1UMR 218 CNRS, Institut Curie, Institut Curie – Section de Recherche, 26 rue d'Ulm, 75248 Paris Cedex 05, France. Cancer Cell Int. 2003; 3: 11.