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

John A. Martignetti, Bruce D. Gelb, Heather Pierce, Piero Picci, Robert J. Desnick

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)191-195
Number of pages5
JournalGenes Chromosomes and Cancer
Volume27
Issue number2
DOIs
Publication statusPublished - Feb 2000

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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