Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Mar;148(3):731–738.

Single somatic ras gene point mutation in soft tissue malignant fibrous histiocytomas.

R M Bohle 1, S Brettreich 1, R Repp 1, A Borkhardt 1, H Kosmehl 1, H M Altmannsberger 1
PMCID: PMC1861737  PMID: 8774129

Abstract

The frequency of ras gene mutations in human soft tissue malignant fibrous histiocytomas within and around the hot spot codons (12, 13, and 61) of all ras genes, (H-ras-1, K-ras-2, and N-ras) was studied by nested polymerase chain reaction and direct DNA sequencing from archival formalin-fixed, paraffin-embedded tissue. Light microscopy and immunohistochemistry served to define malignant fibrous histiocytoma. All of the four differentiation subtypes (storiform-pleomorphic, inflammatory, myxoid, and giant cell) were investigated. Nine of thirty-two malignant fibrous histiocytomas (28%) contained ras gene point mutations. The highest incidence was found in the myxoid subtype (four of nine). H-ras-1 gene codon 12.2 was the only codon affected and contained in all mutated cases a GGC-->GTC exchange. Seven of the nine mutations were homozygous and probably affected more than 80% of the tumor DNA. The flanking regions of all hotspot codons did not contain any point mutation. The presence of a single and often homozygous point mutation of the H-ras-1 gene, especially in myxoid malignant fibrous histiocytoma could serve as a basis for further genomic discrimination of myxoid sarcomas.

Full text

PDF
736

Images in this article

735Figure 1
on p.735

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albert J., Fenyö E. M. Simple, sensitive, and specific detection of human immunodeficiency virus type 1 in clinical specimens by polymerase chain reaction with nested primers. J Clin Microbiol. 1990 Jul;28(7):1560–1564. doi: 10.1128/jcm.28.7.1560-1564.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Almoguera C., Shibata D., Forrester K., Martin J., Arnheim N., Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988 May 20;53(4):549–554. doi: 10.1016/0092-8674(88)90571-5. [DOI] [PubMed] [Google Scholar]
  3. Bar-Sagi D., Feramisco J. R. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985 Oct;42(3):841–848. doi: 10.1016/0092-8674(85)90280-6. [DOI] [PubMed] [Google Scholar]
  4. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  5. Benhattar J., Losi L., Chaubert P., Givel J. C., Costa J. Prognostic significance of K-ras mutations in colorectal carcinoma. Gastroenterology. 1993 Apr;104(4):1044–1048. doi: 10.1016/0016-5085(93)90272-e. [DOI] [PubMed] [Google Scholar]
  6. Bos J. L. ras oncogenes in human cancer: a review. Cancer Res. 1989 Sep 1;49(17):4682–4689. [PubMed] [Google Scholar]
  7. Capon D. J., Chen E. Y., Levinson A. D., Seeburg P. H., Goeddel D. V. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33–37. doi: 10.1038/302033a0. [DOI] [PubMed] [Google Scholar]
  8. Cardiff R. D., Leder A., Kuo A., Pattengale P. K., Leder P. Multiple tumor types appear in a transgenic mouse with the ras oncogene. Am J Pathol. 1993 Apr;142(4):1199–1207. [PMC free article] [PubMed] [Google Scholar]
  9. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  10. Gill S., Stratton M. R., Patterson H., Spurr N. K., Fisher C., Gusterson B. A., Cooper C. S. Detection of transforming genes by transfection of DNA from primary soft-tissue tumours. Oncogene. 1991 Sep;6(9):1651–1656. [PubMed] [Google Scholar]
  11. Gustmann C., Altmannsberger M., Osborn M., Griesser H., Feller A. C. Cytokeratin expression and vimentin content in large cell anaplastic lymphomas and other non-Hodgkin's lymphomas. Am J Pathol. 1991 Jun;138(6):1413–1422. [PMC free article] [PubMed] [Google Scholar]
  12. HARVEY J. J. AN UNIDENTIFIED VIRUS WHICH CAUSES THE RAPID PRODUCTION OF TUMOURS IN MICE. Nature. 1964 Dec 12;204:1104–1105. doi: 10.1038/2041104b0. [DOI] [PubMed] [Google Scholar]
  13. Hallowes R. C., Chesterman F. C. Histochemistry of giant cells in tumours induced in golden hamsters by murine sarscoma virus-Harvey. Int J Cancer. 1971 May 15;7(3):507–512. doi: 10.1002/ijc.2910070317. [DOI] [PubMed] [Google Scholar]
  14. Hallowes R. C., Chesterman F. C. Ultrastructure of giant cells in tumours induced in golden hamsters by murine sarcoma virus-Harvey. Int J Cancer. 1971 May 15;7(3):513–525. doi: 10.1002/ijc.2910070318. [DOI] [PubMed] [Google Scholar]
  15. Hallowes R. C., Chesterman F. C., West D. G. The histogenesis of tumours induced in golden hamsters by murine sarcoma virus-Harvey (MSV-H). Int J Cancer. 1973 Nov 15;12(3):705–721. doi: 10.1002/ijc.2910120318. [DOI] [PubMed] [Google Scholar]
  16. Heller M. J., Burgart L. J., TenEyck C. J., Anderson M. E., Greiner T. C., Robinson R. A. An efficient method for the extraction of DNA from formalin-fixed, paraffin-embedded tissue by sonication. Biotechniques. 1991 Sep;11(3):372-4, 376-7. [PubMed] [Google Scholar]
  17. Hoorens A., Lemoine N. R., McLellan E., Morohoshi T., Kamisawa T., Heitz P. U., Stamm B., Rüschoff J., Wiedenmann B., Klöppel G. Pancreatic acinar cell carcinoma. An analysis of cell lineage markers, p53 expression, and Ki-ras mutation. Am J Pathol. 1993 Sep;143(3):685–698. [PMC free article] [PubMed] [Google Scholar]
  18. Hultman T., Ståhl S., Hornes E., Uhlén M. Direct solid phase sequencing of genomic and plasmid DNA using magnetic beads as solid support. Nucleic Acids Res. 1989 Jul 11;17(13):4937–4946. doi: 10.1093/nar/17.13.4937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Konieczny S. F., Drobes B. L., Menke S. L., Taparowsky E. J. Inhibition of myogenic differentiation by the H-ras oncogene is associated with the down regulation of the MyoD1 gene. Oncogene. 1989 Apr;4(4):473–481. [PubMed] [Google Scholar]
  20. Krengel U., Schlichting I., Scherer A., Schumann R., Frech M., John J., Kabsch W., Pai E. F., Wittinghofer A. Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell. 1990 Aug 10;62(3):539–548. doi: 10.1016/0092-8674(90)90018-a. [DOI] [PubMed] [Google Scholar]
  21. McCormick F. Signal transduction. How receptors turn Ras on. Nature. 1993 May 6;363(6424):15–16. doi: 10.1038/363015a0. [DOI] [PubMed] [Google Scholar]
  22. McGrath J. P., Capon D. J., Smith D. H., Chen E. Y., Seeburg P. H., Goeddel D. V., Levinson A. D. Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature. 1983 Aug 11;304(5926):501–506. doi: 10.1038/304501a0. [DOI] [PubMed] [Google Scholar]
  23. McKenzie S. J. Diagnostic utility of oncogenes and their products in human cancer. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):193–214. doi: 10.1016/0304-419x(91)90014-c. [DOI] [PubMed] [Google Scholar]
  24. Repp R., Rhiel S., Heermann K. H., Schaefer S., Keller C., Ndumbe P., Lampert F., Gerlich W. H. Genotyping by multiplex polymerase chain reaction for detection of endemic hepatitis B virus transmission. J Clin Microbiol. 1993 May;31(5):1095–1102. doi: 10.1128/jcm.31.5.1095-1102.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ridley A. J., Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992 Aug 7;70(3):389–399. doi: 10.1016/0092-8674(92)90163-7. [DOI] [PubMed] [Google Scholar]
  26. Rodenhuis S., Slebos R. J. Clinical significance of ras oncogene activation in human lung cancer. Cancer Res. 1992 May 1;52(9 Suppl):2665s–2669s. [PubMed] [Google Scholar]
  27. Rodenhuis S. ras and human tumors. Semin Cancer Biol. 1992 Aug;3(4):241–247. [PubMed] [Google Scholar]
  28. Seeburg P. H., Colby W. W., Capon D. J., Goeddel D. V., Levinson A. D. Biological properties of human c-Ha-ras1 genes mutated at codon 12. Nature. 1984 Nov 1;312(5989):71–75. doi: 10.1038/312071a0. [DOI] [PubMed] [Google Scholar]
  29. Spandidos D. A., Anderson M. L. Oncogenes and onco-suppressor genes: their involvement in cancer. J Pathol. 1989 Jan;157(1):1–10. doi: 10.1002/path.1711570102. [DOI] [PubMed] [Google Scholar]
  30. Wilke W., Maillet M., Robinson R. H-ras-1 point mutations in soft tissue sarcomas. Mod Pathol. 1993 Mar;6(2):129–132. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES