Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22

Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is an autosomal dominant bone dysplasia/cancer syndrome of unknown etiolog y. This rare hereditary cancer syndrome is characterized by bone infarction s, cortical growth abnormalities, pathological fractures, and eventual pain ful debilitation. Notably, 35% of individuals with DMS develop MFH, a highl y malignant bone sarcoma. A genome scan for the DMS-MFH gene locus in three unrelated families with DMS-MFH linked the syndrome to a region of similar to 3 cM on chromosome 9p21-22, with a maximal two-point LOD score of 5.49 (marker D9S171 at recombination fraction [theta] .05). Interestingly, this region had previously been shown to be the site of chromosomal abnormalitie s in several other malignancies and contains a number of genes whose protei n products are involved in growth regulation. Identification of this rare f amilial sarcoma-causing gene would be expected to simultaneously define the cause of the more common nonfamilial, or sporadic, form of MFH-a tumor tha t constitutes similar to 6% of all bone cancers and is the most frequently occurring adult soft-tissue sarcoma.