Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1996-06-03
2000-01-04
Hutzell, Paula K.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
536 231, 5303881, 5303888, 53038885, 5303891, G01J 3353, C07H 2102, C07K 1600
Patent
active
060108657
DESCRIPTION:
BRIEF SUMMARY
The invention relates to processes for diagnosing and/or analysing tumours by evaluating the expression of variable exons of the CD44-gene, agents for such processes and the use thereof.
There is a need for improved methods of diagnosing and/or analysing cancers, particularly on the basis of molecular markers.
For example, the haematogenic spread of mammary carcinomas occurs very early in the course of the disease and is connected with the later occurrence of remote metastases (Diel et al., 1992). The molecular mechanisms of metastatic spread are still unknown. The prognostic factors for predicting the risk of metastasis are currently based mainly on pathological criteria, the main factors being the stage of the tumour, differentiation (gradation) and lymph node metastasis (Fisher et al., 1990). However, in individual cases, there are discrepancies between these factors, e.g. where in spite of a highly advance tumour size or low differentiation (high gradation) there are no lymph node metastases. Little investigation has been carried out into a subgroup or patients suffering from lymph-node-negative breast cancer who later develop remote metastases. There is therefore a need for parameters which allow better prediction of the haematogenic tumour spread and better general prognosis. Another example consists of stomach tumours. These can be divided into two main histological categories, the intestinal type and the diffuse type (Lauren, 1965). Tumours of the intestinal type but not of the diffuse type are often accompanied by chronic gastritis B and particularly by intestinal metaplasias, which are regarded as precursors of dysplastic changes and adenocarcinomas of the intestinal type (Jida et Kusama, 1982; Jass, 1983; Kato et al., 1981; Sipponen et al., 1983; Sirula et al., 1974; Strickland et Mackay, 1973). Pathogenetic differences between these two types of adenocarcinoma are also reflected in the observation that patients with tumours of the diffuse type often belong to blood group A, which indicates a possible influence of genetic factors on the risk of cancer (Piper, 1978), whereas environmental factors such as infections with Helicobacter pylori may be important in the development of tumours of the intestinal type (Parsonnet et al., 1991; Nomura et al., 1991). It would be desirable to be able to distinguish between tumours of the intestinal type and those of the diffuse type by means of molecular markers. Finally, cervical carcinoma of the uterus may be mentioned as a third example. In spite of a decreasing incidence (Petterson, 1988) the prognosis for patients with advanced stages of cervical carcinomas is poor (Perez et al., 1983; Park et Thigpen, 1993; Brady et al., 1986). Early diagnosis is based on the assessment of early morphological changes in the epithelial cells (cervical smear). Here again it is desirable to discover definite molecular markers for early cancer detection which can be used for staging and as prognostic factors.
It has recently been shown that the expression of variants of the surface glycoprotein CD44 is necessary and sufficient to trigger so-called spontaneous metastatic behaviour both in a non-metastasising pancreas adenocarcinoma cell line in rats and also in a non-metastasising fibrosarcoma cell line in rats (Gunthert et al., 1991). Whereas the smallest CD44-isoform, the standard form CD44s, is expressed ubiquitously in a series of different tissues, including epithelial cells, certain splice variants of CD44 (CD44v) are expressed only on a subgroup of epithelial cells. The CD44-isoforms are produced by alternative splicing so that the sequences of 10 exons (v1-v10) in CD44s are excised completely, but in the larger variants they may occur in different combinations (Screaton et al., 1992; Heider et al., 1993; Hofmann et al., 1991). The variants differ in that different amino acid sequences are inserted at a specific point in the extracellular part of the protein. These variants can be detected in different human tumour cells and in human tumour tissue. Thus, the expression
REFERENCES:
Rudzki et al (J. Clin Pathol. Mol. Pathol, 50:57-71, 1997.
Zoller (JMM, 73:425-438), 1995.
Strong in (Laboratory Diagnosis of Viral Infections, 2d Ed, E. Lennetto Ed. Marcel Dekker, Inc., NY. pp. 211-219, 1992.
Dall, et al (Cancer Res., 54:3337-3341, 1994.
Woerner et al (Clin Cancer Res, 1:1125-1132), 1995.
Woodman et al (Am. J. Pathol, 149:1519-1530, 1996.
Matsumura et al (Lancet, 340:1053-1058, 1992.
Cannistra et al (J. Clin Oncol, 13:1912-1921, 1995.
Screaton et al (PNAS, 89:12160-12164), 1992.
Tempfer et al (Cancer, 1996, 78:273-277).
Johnstone & Thorpe (Immunochemistry in Practice 2nd Ed. Blackwell Scientific Pub. Oxford, p. 30), 1987.
Huse (Science, 246:1275-1281, 1989.
Hofmann et al (Cancer Res, 51:5292-5297, 1991.
Smith et al., Alternative Splicing in the Control of Gene Expression, Annu. Rev. Genet., vol. 23:527-77 (1989).
Dall Peter
Heider Karl-Heinz
Herrlich Peter
Pals Steven T.
Ponta Helmut
Boehringer Ingelheim International GmbH
Hutzell Paula K.
Ungar Susan
LandOfFree
Process for detecting a variant CD44 gene product does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for detecting a variant CD44 gene product, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for detecting a variant CD44 gene product will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1071711