hSNF5/INI1 inactivation is mainly associated with homozygous deletions andmitotic recombinations in rhabdoid tumors

The chromatin-remodeling hSNF5/INI1 gene has recently been shown to act as a tumor suppressor gene in rhabdoid tumors (RTs),In an attempt to further c haracterize the main chromosomal mechanisms involved in hSNF5/INI1 inactiva tion in RTs, cre report here the molecular cytogenetic data obtained in 12 cell lines harboring hSNF5/INI1 mutations and/or deletions in relation to t he molecular genetic analysis using polymorphic markers extended to both ex tremities of chromosome 22q, On the whole, mitotic recombination occurring in the proximal part of chromosome 22q, as demonstrated in five cases, and nondisjunction/duplication, highly suspected in two cases (processes leadin g respectively to partial or complete isodisomy), appear to be major mechan isms associated with hSNF5/INI1 inactivation. Such isodisomy accompanies ea ch of the RTs exhibiting two cytogenetically normal chromosomes 22, This re sults in homozygosity for the mutation at the hSNF5/INI1 locus. An alternat e mechanism accounting for hSNF5/INI1 inactivation observed in these tumors is homozygous deletion in the rhabdoid consensus region. This was observed in each of the four tumors carrying a chromosome 22q abnormality and, in p articular, in the three tumors with chromosomal translocations. Only one ca se of our series illustrates the mutation/deletion classical model proposed for the double-hit inactivation of a tumor suppressor gene.