Ras oncogene mutation in multiple myeloma

A. Neri, J. P. Murphy, L. Cro, D. Ferrero, C. Tarella, L. Baldini, R. Dalla-Favera

Research output: Contribution to journalArticle

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Abstract

The frequency of ras (H-, K-, and N-ras) and c-myc oncogenes was investigated in multiple myeloma (MM). By means of the polymerase chain reaction (PCR)/oligonucleotide hybridization method, DNA from 56 tumor biopsies was analyzed for the presence of activating mutations involving codons 12 and 61 of the H-, K-, and N-ras genes and codon 13 of the N-ras gene. Mutations, involving the N- or K-ras genes, were detected in 18 of 56 (32%) cases of which 12/43 (27%) were at diagnosis and 6/13 (46%) were after treatment. In some cases, multiple mutations affecting different ras alleles were detected. Direct nucleotide sequence analysis of PCR products indicated that a more heterogeneous nature of the base pair changes than previously shown for other tumors along with a preferential involvement of N-ras codon 61. The heterogeneity of MM cases with respect to the presence of ras oncogenes prompted an analysis of possible correlations with different clinico-pathologic characteristics of MM from which a correlation between the presence of ras oncogenes and a partial or complete lack of response to therapy emerged. The frequency of activating rearrangements or mutations of the c-myc gene were studied by Southern blot analysis and PCR sequencing, respectively. However, contrary to previous reports involving mostly MM cell lines, no structural alterations of the c-myc gene were found. These results indicate that ras, but not c-myc, oncogenes are activated in vivo in MM cells, representing the first oncogene alteration that has been associated at appreciable frequency with this type of malignancy. While the mechanism of occurrence and biological role of ras activation in MM remains to be elucidated, the preliminary correlations observed in this study between the presence of ras oncogenes and poor therapeutic response suggest that further investigations of the possible prognostic significance of these alterations are necessary.

Original languageEnglish
Pages (from-to)1715-1725
Number of pages11
JournalJournal of Experimental Medicine
Volume170
Issue number5
Publication statusPublished - 1989

Fingerprint

ras Genes
Multiple Myeloma
myc Genes
Mutation
Codon
Polymerase Chain Reaction
Neoplasms
Southern Blotting
Oncogenes
Oligonucleotides
Base Pairing
Sequence Analysis
Alleles
Biopsy
Cell Line
DNA
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Neri, A., Murphy, J. P., Cro, L., Ferrero, D., Tarella, C., Baldini, L., & Dalla-Favera, R. (1989). Ras oncogene mutation in multiple myeloma. Journal of Experimental Medicine, 170(5), 1715-1725.

Ras oncogene mutation in multiple myeloma. / Neri, A.; Murphy, J. P.; Cro, L.; Ferrero, D.; Tarella, C.; Baldini, L.; Dalla-Favera, R.

In: Journal of Experimental Medicine, Vol. 170, No. 5, 1989, p. 1715-1725.

Research output: Contribution to journalArticle

Neri, A, Murphy, JP, Cro, L, Ferrero, D, Tarella, C, Baldini, L & Dalla-Favera, R 1989, 'Ras oncogene mutation in multiple myeloma', Journal of Experimental Medicine, vol. 170, no. 5, pp. 1715-1725.
Neri A, Murphy JP, Cro L, Ferrero D, Tarella C, Baldini L et al. Ras oncogene mutation in multiple myeloma. Journal of Experimental Medicine. 1989;170(5):1715-1725.
Neri, A. ; Murphy, J. P. ; Cro, L. ; Ferrero, D. ; Tarella, C. ; Baldini, L. ; Dalla-Favera, R. / Ras oncogene mutation in multiple myeloma. In: Journal of Experimental Medicine. 1989 ; Vol. 170, No. 5. pp. 1715-1725.
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