Evaluation of the tyrosine kinase domain of theMet Proto-oncogene in sporadic ovarian carcinomas

Most of the ovarian cancers originate from the ovarian surface epithelium derived from the coelomic mesothelium. TheMet proto-oncogene encodes a transmembrane tyrosine kinase receptor (Met) that has the capacity to regulate cell proliferation and differentation and it is activated by hepatocyte growth factor. Trisomy of chromosome 7 and Met protein overexpression have been were observed in ovarian carcinomas, the papillary renal cancers and other solid tumors. Frequent mutations ofMet proto-oncogene have been found in hereditary papillary renal cancer (HPRC) and most of the mutations are located in the tyrosine kinase domain. The aim of this study to perform a mutation analysis of exons 17-19 ofMet proto-oncogene in epithelial ovarian tumors (EOTs). We have examined 24 tumor samples from patients, operated with EOTs. Mutation was detected in exon 18 in only one sample of 24 EOTs. Our results indicate that mutations located in theMet proto-oncogene is not a common event in EOT. It is not clear whether the mutation plays a role in the tumorigenesis or progression of EOT or not.

[1]  W. Marston Linehan,et al.  Trisomy 7-harbouring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas , 1998, Nature Genetics.

[2]  S. Scherer,et al.  Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas , 1997, Nature Genetics.

[3]  F. Mitelman,et al.  Karyotypic characteristics of borderline malignant tumors of the ovary: trisomy 12, trisomy 7, and r(1) as nonrandom features. , 1996, Cancer genetics and cytogenetics.

[4]  P. Comoglio,et al.  Overexpression of the met/HGF receptor in renal cell carcinomas , 1996, International journal of cancer.

[5]  G. V. Vande Woude,et al.  Enhanced tumorigenicity and invasion-metastasis by hepatocyte growth factor/scatter factor-met signalling in human cells concomitant with induction of the urokinase proteolysis network , 1996, Molecular and cellular biology.

[6]  Carmen Birchmeier,et al.  Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud , 1995, Nature.

[7]  al. et,et al.  Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B , 1995, Science.

[8]  M. Noble,et al.  Roles of hepatocyte growth factor/scatter factor and the met receptor in the early development of the metanephros , 1995, The Journal of cell biology.

[9]  H. Friess,et al.  Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer. , 1994, Cancer research.

[10]  P Zola,et al.  Overexpression of the MET/HGF receptor in ovarian cancer , 1994, International journal of cancer.

[11]  E. Rosen,et al.  Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epi , 1994, The Journal of clinical investigation.

[12]  R. Hofstra,et al.  A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma , 1994, Nature.

[13]  C. Birchmeier,et al.  Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development , 1993, The Journal of cell biology.

[14]  W. Birchmeier,et al.  The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells , 1993, The Journal of cell biology.

[15]  R. Berkowitz,et al.  Mutation of K-ras protooncogene in human ovarian epithelial tumors of borderline malignancy. , 1993, Cancer research.

[16]  L. Hartmann,et al.  Interphase molecular cytogenetic analysis of epithelial ovarian carcinomas. , 1993, The American journal of pathology.

[17]  M. Pierotti,et al.  Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. , 1992, Oncogene.

[18]  A. Bardelli,et al.  Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. , 1991, The EMBO journal.

[19]  N. Fausto.  Hepatocyte growth factor receptor and the c-met oncogene Bottaro DP, Rubin JS, Faletto DL, Chan AM-L, Kmiecik TE, Vande Woude GF, Aaronson SA. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 1991;251:802?804 , 1991 .

[20]  P. Comoglio,et al.  The receptor encoded by the human C‐MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors , 1991, International journal of cancer.

[21]  R. Ozols,et al.  Ovarian cancer biology. , 1991, Seminars in oncology.

[22]  J. Rubin,et al.  Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. , 1991, Science.

[23]  C. Cooper,et al.  Tyrosine kinase receptor indistinguishable from the c-met protein , 1989, Nature.

[24]  R. Kurzrock,et al.  Trisomy 12 correlates with elevated expression of p21 ras in a human adenosquamous carcinoma of the lung. , 1986, Cancer genetics and cytogenetics.

[25]  H. Battifora,et al.  Rhabdomyoma of larynx: Ultrastructural study and comparison with granular cell tumors (myoblastomas) , 1969, Cancer.

[26]  G. Kovacs,et al.  Molecular cytogenetics of renal cell tumors. , 1993, Advances in cancer research.