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. 1999 Mar;64(3):801–807. doi: 10.1086/302297

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

J A Martignetti 1, R J Desnick 1, E Aliprandis 1, K I Norton 1, P Hardcastle 1, S Nade 1, B D Gelb 1
PMCID: PMC1377798  PMID: 10053015

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.

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Selected References

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  1. Adams P. LABMAN and LINKMAN: a data management system specifically designed for genome searches of complex diseases. Genet Epidemiol. 1994;11(1):87–98. doi: 10.1002/gepi.1370110109. [DOI] [PubMed] [Google Scholar]
  2. Anderson M. A., Gusella J. F. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro. 1984 Nov;20(11):856–858. doi: 10.1007/BF02619631. [DOI] [PubMed] [Google Scholar]
  3. Arnold W. H. Hereditary bone dysplasia with sarcomatous degeneration. Study of a family. Ann Intern Med. 1973 Jun;78(6):902–906. doi: 10.7326/0003-4819-78-6-902. [DOI] [PubMed] [Google Scholar]
  4. Brinck U., Stachura J., Rudzki Z., Kellner S., Hoefer K., Schauer A. P-53 positivity and high proliferative index: factors of bad prognosis in malignant fibrous histiocytomas. In Vivo. 1995 Sep-Oct;9(5):475–478. [PubMed] [Google Scholar]
  5. Bun-Ya M., Harashima S., Oshima Y. Putative GTP-binding protein, Gtr1, associated with the function of the Pho84 inorganic phosphate transporter in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Jul;12(7):2958–2966. doi: 10.1128/mcb.12.7.2958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cannon-Albright L. A., Goldgar D. E., Neuhausen S., Gruis N. A., Anderson D. E., Lewis C. M., Jost M., Tran T. D., Nyguen K., Kamb A. Localization of the 9p melanoma susceptibility locus (MLM) to a 2-cM region between D9S736 and D9S171. Genomics. 1994 Sep 1;23(1):265–268. doi: 10.1006/geno.1994.1491. [DOI] [PubMed] [Google Scholar]
  7. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  8. Fearon E. R. Human cancer syndromes: clues to the origin and nature of cancer. Science. 1997 Nov 7;278(5340):1043–1050. doi: 10.1126/science.278.5340.1043. [DOI] [PubMed] [Google Scholar]
  9. Fountain J. W., Karayiorgou M., Taruscio D., Graw S. L., Buckler A. J., Ward D. C., Dracopoli N. C., Housman D. E. Genetic and physical map of the interferon region on chromosome 9p. Genomics. 1992 Sep;14(1):105–112. doi: 10.1016/s0888-7543(05)80290-3. [DOI] [PubMed] [Google Scholar]
  10. Gelb B. D., Edelson J. G., Desnick R. J. Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping. Nat Genet. 1995 Jun;10(2):235–237. doi: 10.1038/ng0695-235. [DOI] [PubMed] [Google Scholar]
  11. Gruis N. A., van der Velden P. A., Sandkuijl L. A., Prins D. E., Weaver-Feldhaus J., Kamb A., Bergman W., Frants R. R. Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds. Nat Genet. 1995 Jul;10(3):351–353. doi: 10.1038/ng0795-351. [DOI] [PubMed] [Google Scholar]
  12. Harada H., Hashimoto K., Ko M. S. The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J Invest Dermatol. 1996 Jul;107(1):41–43. doi: 10.1111/1523-1747.ep12297860. [DOI] [PubMed] [Google Scholar]
  13. Hardcastle P., Nade S., Arnold W. Hereditary bone dysplasia with malignant change. Report of three families. J Bone Joint Surg Am. 1986 Sep;68(7):1079–1089. [PubMed] [Google Scholar]
  14. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  15. Larramendy M. L., Tarkkanen M., Blomqvist C., Virolainen M., Wiklund T., Asko-Seljavaara S., Elomaa I., Knuutila S. Comparative genomic hybridization of malignant fibrous histiocytoma reveals a novel prognostic marker. Am J Pathol. 1997 Oct;151(4):1153–1161. [PMC free article] [PubMed] [Google Scholar]
  16. Murray J. C., Buetow K. H., Weber J. L., Ludwigsen S., Scherpbier-Heddema T., Manion F., Quillen J., Sheffield V. C., Sunden S., Duyk G. M. A comprehensive human linkage map with centimorgan density. Cooperative Human Linkage Center (CHLC). Science. 1994 Sep 30;265(5181):2049–2054. doi: 10.1126/science.8091227. [DOI] [PubMed] [Google Scholar]
  17. Nakamura T., Alder H., Gu Y., Prasad R., Canaani O., Kamada N., Gale R. P., Lange B., Crist W. M., Nowell P. C. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4631–4635. doi: 10.1073/pnas.90.10.4631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Norton K. I., Wagreich J. M., Granowetter L., Martignetti J. A. Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): Hardcastle syndrome. Pediatr Radiol. 1996 Sep;26(9):675–677. doi: 10.1007/BF01356833. [DOI] [PubMed] [Google Scholar]
  19. Reid A. H., Tsai M. M., Venzon D. J., Wright C. F., Lack E. E., O'Leary T. J. MDM2 amplification, P53 mutation, and accumulation of the P53 gene product in malignant fibrous histiocytoma. Diagn Mol Pathol. 1996 Mar;5(1):65–73. doi: 10.1097/00019606-199603000-00010. [DOI] [PubMed] [Google Scholar]
  20. Schürmann A., Brauers A., Massmann S., Becker W., Joost H. G. Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases. J Biol Chem. 1995 Dec 1;270(48):28982–28988. doi: 10.1074/jbc.270.48.28982. [DOI] [PubMed] [Google Scholar]
  21. Stadler W. M., Sherman J., Bohlander S. K., Roulston D., Dreyling M., Rukstalis D., Olopade O. I. Homozygous deletions within chromosomal bands 9p21-22 in bladder cancer. Cancer Res. 1994 Apr 15;54(8):2060–2063. [PubMed] [Google Scholar]
  22. Szymanska J., Tarkkanen M., Wiklund T., Virolainen M., Blomqvist C., Asko-Seljavaara S., Tukiainen E., Elomaa I., Knuutila S. A cytogenetic study of malignant fibrous histiocytoma. Cancer Genet Cytogenet. 1995 Dec;85(2):91–96. doi: 10.1016/0165-4608(95)00143-3. [DOI] [PubMed] [Google Scholar]
  23. Trent J. M., Olson S., Lawn R. M. Chromosomal localization of human leukocyte, fibroblast, and immune interferon genes by means of in situ hybridization. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7809–7813. doi: 10.1073/pnas.79.24.7809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Walter T. A., Weh H. J., Schlag P. M., Zornig C., Hossfeld D. K. Cytogenetic studies in malignant fibrous histiocytoma. Cancer Genet Cytogenet. 1997 Apr;94(2):131–134. doi: 10.1016/s0165-4608(96)00220-8. [DOI] [PubMed] [Google Scholar]
  25. Xu G., O'Connell P., Stevens J., White R. Characterization of human adenylate kinase 3 (AK3) cDNA and mapping of the AK3 pseudogene to an intron of the NF1 gene. Genomics. 1992 Jul;13(3):537–542. doi: 10.1016/0888-7543(92)90122-9. [DOI] [PubMed] [Google Scholar]

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