Human CrkRS-related gene variant associated with lung cancers

#The invention relates to the nucleic acid of a novel human CrkRs-related gene variant, the polypeptide encoded thereby, the preparation process thereof, and the uses of the same in diagnosing diseases associated with the deficiency of CrkRS gene, in particular, lung cancers.

#Lung cancer is one of the major causers of cancer-related deaths in the world. There are two primary types of lung cancers: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) (Carney, (1992a) Curr. Opin. Oncol. 4:292-8). Small cell lung cancer accounts for approximately 25% of lung cancer and spreads aggressively (Smyth et al. (1986) Q J Med. 61: 969-76; Carney, (1992b) Lancet 339: 843-6). Non-small cell lung cancer represents the majority (about 75%) of lung cancer and is further divided into three main subtypes: squamous cell carcinoma, adenocarcinoma, and large cell carcinoma (Ihde and Minna, (1991) Cancer 15: 105-54). In recent years, much progress has been made toward understanding the molecular and cellular biology of lung cancers. Many important contributions have been made by the identification of several key genetic factors associated with lung cancers. However, the treatments of lung cancers still mainly depend on surgery, chemotherapy, and radiotherapy. This is because the molecular mechanisms underlying the pathogenesis of lung cancers remain largely unclear.

#A recent hypothesis suggested that lung cancer is caused by genetic mutations of at least 10 to 20 genes (Sethi, (1997) BMJ. 314: 652-655). Therefore, future strategies for the prevention and treatment of lung cancers will be focused on the elucidation of these genetic substrates, in particular, the genes localized on chromosome 17, a region shown to be associated with the development of lung cancer (Sameshima et al. (1990) Biochem Biophys Res Commun 173:697-703; Kato et al. (1993) Jpn J Cancer Res 84:355-9; Shimizu et al. (1993) Cancer 71:725-8; Levin et al. (1995) Genes Chromosomes Cancer 13:175-85; Abujiang et al. (1998) Oncogene 17:3029-33; Konishi et al. (1998) Oncogene 17:2095-100). Recently, CrkRS (a novel human protein kinase, Cdc2-related kinase with arginine/serine-rich domain) transcript mapped on this region (Ko et al. (2001) J Cell Sci 114:2591-603) raised a possibility that this novel gene may have a role in the tumorigenic process of lung cancer. Therefore, the discovery of gene variants of CrkRS may be important targets for diagnostic markers of lung cancer.

#FIG. 1 shows the nucleic acid sequence (SEQ ID NO:1) and amino acid sequence (SEQ ID NO:2) of CrkRSV.

#FIG. 2 shows the nucleotide sequence alignment between the human CrkRS gene and CrkRSV.

#FIG. 3 shows the amino acid sequence alignment between the human CrkRS protein and CrkRSV.

#According to the present invention, all technical and scientific terms used have the same meanings as commonly understood by persons skilled in the art.

#The term “antibody” used herein denotes intact molecules (a polypeptide or group of polypeptides) as well as fragments thereof, such as Fab, R(ab′)2, and Fv fragments, which are capable of binding the epitopic determinant. Antibodies are produced by specialized B cells after stimulation by an antigen. Structurally, antibody consists of four subunits including two heavy chains and two light chains. The internal surface shape and charge distribution of the antibody binding domain is complementary to the features of an antigen. Thus, antibody can specifically act against the antigen in an immune response.

#The term “base pair (bp)” used herein denotes nucleotides composed of a purine on one strand of DNA which can be hydrogen bonded to a pyrimidine on the other strand. Thymine (or uracil) and adenine residues are linked by two hydrogen bonds. Cytosine and guanine residues are linked by three hydrogen bonds.