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 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.
Martignetti
J A
JA
Department of Human Genetics, Mount Sinai School of Medicine, Box 1498, Fifth Avenue at 100th Street, New York, NY 10029, USA jam@msvax.mssm.edu
Desnick
R J
RJ
Aliprandis
E
E
Norton
K I
KI
Hardcastle
P
P
Nade
S
S
Gelb
B D
BD
D001848:Bone Diseases, Developmental / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003001:Cloning, Molecular; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length