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

Abstract

Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is an autosomal dominant bone dysplasia/cancer syndrome of unknown etiology. This rare hereditary cancer syndrome is characterized by bone infarctions, cortical growth abnormalities, pathological fractures, and eventual painful debilitation. Notably, 35% of individuals with DMS develop MFH, a highly 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 approximately 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 abnormalities in several other malignancies and contains a number of genes whose protein products are involved in growth regulation. Identification of this rare familial sarcoma-causing gene would be expected to simultaneously define the cause of the more common nonfamilial, or sporadic, form of MFH-a tumor that constitutes approximately 6% of all bone cancers and is the most frequently occurring adult soft-tissue sarcoma.

• Authors: J A Martignetti, R J Desnick, E Aliprandis, K I Norton, P Hardcastle, S Nade, B D Gelb
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 64 Issue 3 Pg. 801-7 (Mar 1999) ISSN: 0002-9297 [Print] United States
• PMID: 10053015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Topics

• Bone Diseases, Developmental (genetics)
• Cell Line
• Chromosome Mapping
• Chromosomes, Human, Pair 9 (genetics)
• Cloning, Molecular
• Genes, Dominant
• Genetic Linkage
• Haplotypes
• Histiocytoma, Benign Fibrous (genetics)
• Humans
• Lod Score
• Neoplastic Syndromes, Hereditary (genetics)
• Pedigree
• Polymorphism, Restriction Fragment Length