title: Malignant fibrous histiocytoma: inherited and sporadic forms have loss of heterozygosity at chromosome bands 9p21-22-evidence for a common genetic defect.
abstract: Hereditary cancers represent a unique opportunity to investigate the genetic etiology of their more common sporadic forms. We recently established genetic linkage for the rare autosomal-dominant bone dysplasia/cancer syndrome, diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH), to a 3-cM region on chromosome bands 9p21-22. This hereditary cancer syndrome is characterized by bone infarctions, cortical growth abnormalities, pathologic fractures, and painful debilitation. Most notably, 35% of affected individuals develop bone MFH, a sarcoma that, in its sporadic form, accounts for 6% of all bone cancers. To determine whether the hereditary and sporadic forms of bone MFH are genetically linked, we performed loss of heterozygosity (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 minimal region of LOH overlap effectively limited the DMS-MFH gene to a 2-cM region between markers D9S736 and D9S171. In summary, these studies suggest that a common genetic etiology underlies the autosomal-dominant and sporadic forms of this sarcoma and provide the basis for identifying the putative MFH tumor suppressor gene. Genes Chromosomes Cancer 27:191-195, 2000.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, New York,NY 10029, USA. jam@msvax.mssm.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Martignetti
authors.forename: B D
authors.initials: BD
authors.lastname: Gelb
authors.forename: H
authors.initials: H
authors.lastname: Pierce
authors.forename: P
authors.initials: P
authors.lastname: Picci
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001848:Bone Diseases, Developmental / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm