Malignant fibrous histiocytoma: Inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22 - Evidence for a common genetic defect

Hereditary cancers represent a unique opportunity to investigate the geneti c etiology of their more common sporadic forms. We recently established gen etic linkage for the rare autosomal-dominant bone dysplasia/cancer syndrome , diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MF H), to a 3-cM region on chromosome bands 9p21-22. This hereditary cancer sy ndrome is characterized by hone infarctions, cortical growth abnormalities, pathologic fractures, and painful debilitation. Most notably, 35% of affec ted individuals develop bone MFH, a sarcoma that, in its sporadic form, acc ounts for 6% of all bone cancers. To determine whether the hereditary and s poradic forms of bone MFH are genetically linked, we performed loss of hete rozygosity (LOH) studies of the DMS-MFH critical region. In addition to the hereditary specimen, 71% (5/7) of informative sporadic bone MFH specimens displayed LOH for markers within that same region. Definition of the minima l region of LOH overlap effectively limited the DMS-MFH gene to a 2-cM regi on between markers D9S736 and D9S171. In summary, these studies suggest tha t a common genetic etiology underlies the autosomal-dominant and sporadic f orms of this sarcoma and provide the basis for identifying the putative MFH tumor suppressor gene. Genes Chromosomes Cancer 27: 191-195, 2000. (C) 200 0 Wiley-Liss, Inc.