Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1995-01-18
1999-10-19
Arthur, Lisa B.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
530402, 5303871, 530350, 5303881, 536 235, C12Q 168, C07K 1400, C07K 1600, C07H 2104
Patent
active
059687347
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a nucleic acid including all or part of the nucleic sequence of a gene of chromosome 22 involved in the recurrent chromosomal translocations associated with the development of cancerous tumors. The subject of the invention is also hybrid nucleic acids corresponding to the products of fusion resulting from the chromosomal translocations in which this gene of chromosome 22 is involved.
The invention relates more particularly to a nucleic acid including all or part of the nucleic sequence of the gene of chromosome 22 involved in the recurrent chromosomal translocations t(11;22), t(21;22) and t(12;22), as well as the hybrid nucleic acids resulting from the fusion of this gene of chromosome 22 with the genes of chromosomes 11, 21 and 12, respectively, which are involved in these translocations. The invention also relates to the mRNAs originating in the DNA of the gene of chromosome 22 and the fusions DNAs as well as the cDNAs that can derive from them, as well as the proteins for which they code.
The invention also relates to the detection of the gene of chromosome 22 involved in the chromosomal translocations, as well as the fusion genes resulting from these translocations, with the aid of probes prepared on the basis of precursor nucleic acids, with a view to diagnosing Ewing's sarcoma and related tumors in subjects suffering from "small round cell", or small cell, tumors or primitive peripheral neurectodermic tumors, or malignant melanoma of the soft tissues; the invention also relates to the detection, for the same purposes, of products for which these genes code, and the products and reagents for implementing these methods.
Recurrent chromosomal translocations represent a mechanism of oncogene activation and hence are implicated in the appearance of numerous pathogenic tumors (E. Solomon, J. Barrow, A. D. Goddard, Science 254, 1153-1160 (1991)). Among them, those known as small cell tumors represent a group of heterogeneous cancers. Precise diagnosis of these tumors is essential so that the therapeutic protocol to be used to treat them can be chosen correctly. A subset of these tumors involves a chromosomal translocation t(11;22)(q24;12) and is sensitive to the same therapeutic protocol.
Ewing's sarcoma represents the most frequent secondary bone tumor in the child. Despite the lack of a morphological marker, Ewing's sarcoma cells occasionally express antigens or can cause the expression of characteristic morphological traits of neural differentiation (M. Lipinski, K. Braham, I. Philip et al., Cancer Res. 47, 183-187 (1987); A. O. Cavazzana, J. S. Miser, J. Jefferson, T. J. Triche, Am. J. Pathol. 127, 507-518 (1987)). Thus techniques for diagnosing small cell tumors use the conventional methods of anatomopathology and cytology, and hence represent a diagnosis by exclusion, which is not entirely reliable. Demonstrating the presence of a chromosomal translocation t(11;22) in a small cell tumor can be done by a karyotype study; this study requires the cells to arrive at the laboratory alive, which is often difficult to achieve and results in an elevated failure rate; furthermore, there are difficulties in interpretation.
Ewing's sarcoma (ES) has been connected with a subtype of peripheral primitive neurectodermic tumors (PNET) called peripheral neuroepithelioma (PN). This relationship is also supported by the highly specific expression of the MIC2 antigen both in Ewing's sarcoma (ES) and in peripheral neuroepithelioma (PN), while in the majority of other human tumors this antigen is not expressed (I. M. Ambros, P. F. Ambros, S. Strehl et al., Cancer 67, 1886-1893 (1991); P. Garin-Chesa, E. J. Fellinger, A. G. Huvos et al., Am. J. Pathol. 139, 275-286 (1991)). With other rare subtypes of primitive neurectodermic tumors (J. Whang-Peng, C. E. Freter, T. Knutson, J. J. Nanfro, A. Gazdar, Cancer Genet. Cytogenet. 29, 155-258 (1987); J. P. Chadarevian, M. Vekemans, T. A. Seemayer, N. Engl. J. Med. 311, 1702-1703 (1984); A. O. Cavazzana, S. Navarro, R. Noguera et al., Adv. Neuroblast
REFERENCES:
Gura, Science 570: 575-577, 1995.
James, Antiviral Chemistry and Chemostherapy 2: 191-214, 1991.
Gura Science 270: 575-577, 1995.
James, Antiviral Chemistry and Chemotherapy, 2(4) 191-214, 1991.
Guterriez, The Lancet, 339: 715-721, 1992.
Talmadge, Advanced Drug Delivery Reviews, 10 : 247-299, 1993.
Goldberg et al. Clinical Chemistry 39: 2360-2374, 1993.
Freeman, Adv. Drug Delivery Reviews, 12: 169-18, 1993.
Proceedings of the American Association for Cancer Research, vol. 33, Mar. 1992, pp. 604-605--Delattre et al.
Genes & Development, Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fly-1 closely, . . . etc., Ben-David et al, vol. 5, No. 6, pp. 897-1114, Jun. 1991.
Genomics, The Neuroepithelioma Breakpoint on Chromosome 22 Is Proximal to the Meningioma Locus, Zhang et al, vol. 6, No. 1, Jan. 1990.
Nature, Gene Fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours, Delattre et al, vol. 359, Sep. 10, 1992.
Aurias Alain
Delattre Olivier
Desmaze Chantal
Melot Thomas
Peter Martine
(CNRS Centre National de la Recherche Scientifique
Arthur Lisa B.
LandOfFree
Nucleic acid corresponding to a gene of chromosome 22 involved i does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nucleic acid corresponding to a gene of chromosome 22 involved i, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acid corresponding to a gene of chromosome 22 involved i will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2054348