Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1998-11-13
2001-01-09
Fredman, Jeffrey (Department: 1655)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C536S024300, C536S024310, C536S023100, C435S091200
Reexamination Certificate
active
06171791
ABSTRACT:
FIELD OF THE INVENTION
The present invention concerns a novel nucleotide sequence and methods for its use. In particular, the present invention concerns a novel nucleotide sequence which can be used in the diagnosis and treatment of cancer in mammals, in the production of reagents and kits for analysis and pharmaceutical compositions for treatment and/or prevention.
BACKGROUND OF THE INVENTION
Genetic alterations are associated with the genesis of neoplasia and could hence function as markers for early diagnosis of cancer. In all treatment of cancer, regardless of the method of therapy, the ability to identify cancerous tissue and cells is of uttermost importance. The need for substances, specifically binding to cancerous cells is also apparent. Further, the possibility of neutralizing or counteracting said alterations is a key to future prevention and treatment of cancer. Substantive research has been conducted to identify the specific alterations associated with different types of cancer. Only the knowledge of the specific alteration or alterations behind each type of cancer makes possible the use of selective methods in diagnosing, prevention and/or treatment.
PRIOR ART
The RET proto-oncogene encodes a transmembrane receptor tyrosine kinase, whose ligand has recently been identified as glial cell line-derived neurotrophic factor (GDNF) (Durbec et al., 1996; Trupp et al., 1996). Four hereditary diseases with autosomal dominant inheritance have been tied to mutations in the RET gene: familial medullary carcinoma (FMTC) (Farndon et al., 1986; Jackson and Norum, 1989; Lairmore and Wells, 1993); multiple endocrine neoplasia type 2A (MEN 2A) in which patients develop medullary thyroid carcinoma (MTC) and pheochromocytoma, (Sipple, 1961); MEN 2B which shows these two tumors in conjunction with skeletal abnormalities and ganglioneuromas of the gastrointestinal tract (Carney et al., 1976; Schimke et al., 1968), and Hirschprung's disease, shows a congenital lack of enteric plexus neurons resulting in intestinal immobility. In FMTC, germ-line point mutations are found in exons 10, 11, 13, 14 and 16 of the RET proto-oncogene (Bolino et al., 1995; Donis-Keller et al., 1993; Eng et al., 1995; Schuffenecker et al., 1994).
Point mutations in exons 10 and 11 have been reported in association with MEN 2A, while specific missense mutations in exon 16 have been found in MEN 2B and a small proportion of sporadic MTC (Donis-Keller et al., 1993; Eng et al., 1995; Hofstra et al., 1994; Mulligan et al., 1993). In addition, the deletion of six bases removing a cysteine at codon 630 or 634 has been reported in two separate cases of sporadic MTC. (S. Dou and H. Donis-Keller, unpublished results, (Kimura et al., 1995).
SUMMARY OF THE INVENTION
The present inventors have found, that specific deletions are indicative of cancer in cells of neural crest origin and that a specific, previously unknown deletion of nine base pairs in RET exon 11 is indicative of cancer in cells of neural crest origin, e.g. multiple endocrine neoplasia (MEN) type 2A and 2B, pheochromocytoma, enteric ganglioneuromatosis, parathyroid hyperplasia, ganglioneuromas and medullary thyroid cancer (MTC). The present inventors have succeeded in isolating and identifying this deletion and shown its relevance as a specific marker of medullary thyroid cancer. The scope of the invention will be apparent from the claims and the description and examples, which are to be read in connection with the appended figures.
REFERENCES:
Alemi et al. Anticancer Research 16:2619-2622 (1996).*
Alemi Mansour
S{umlaut over (a)}llström Jan
Wilander Erik
C-Einsmann Juliet
Fredman Jeffrey
John Lezdey & Assoc
Karyogene AB
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