The RB1 gene is the target of chromosome 13 deletions in malignant fibroushistiocytoma

Forty-four malignant Fibrous histiocytomas (MFHs) were studied by comparati ve genomic hybridization. Among the observed imbalances, losses of the 13q1 4-q21 region were observed in almost all tumors (78%), suggesting that a ge ne localized in this region could act as a tumor suppressor gene and that i ts inactivation could be relevant for MFH oncogenesis and/or progression. W e determined by CA repeat analyses a consensus region of deletion focusing on the RBI region. The RBI gene was then analyzed by protein truncation tes t, direct sequencing, fluorescence in situ hybridization, Southern blotting , and immunohistochemistry. RBI mutations and/or homozygous deletions were found in 7 of the 34 tumors analyzed (20%). Among the 35 tumors with compar ative genomic hybridization imbalances analyzed by immunohistochemistry, 30 (86%) did not exhibit significant nuclear labeling. The high correlation b etween chromosome 13 losses and absence of RBI protein expression and the m utations detected strongly suggest that RBI gene inactivation is a pivotal event in MFH oncogenesis, Moreover, the observation of a high incidence of MFH in patients previously treated for hereditary retinoblastoma fits well this hypothesis.