title: The Met/hepatocyte growth factor receptor (HGFR) gene is overexpressed in some cases of human leukemia and lymphoma.
abstract: The proto-oncogene c-met encodes a heterodimeric (alpha, beta) tyrosine kinase receptor which binds the hepatocyte growth factor (HGF). Recently, overexpression of the Met/HGF receptor gene has been detected in fresh samples of carcinomas and in epithelial tumor cell lines but not in cell lines derived from human leukemia and lymphoma. Our analysis of 50 primary samples of human leukemia and lymphoma and 23 hematopoietic cell lines revealed expression of mRNA and protein of the met/HGF receptor in 6 out of the 73 hematopoietic tumor samples analyzed. Four of the six samples positive for expression of the Met/HGF receptor gene were derived from patients with Hodgkin's disease. In addition, in one Burkitt's lymphoma cell line and in one acute myeloid leukemia (AML), expression of the Met/HGF receptor gene was detected. In normal unstimulated lymphocytes, granulocytes or monocytes we did not find expression of the Met/HGF receptor gene. Upon stimulation with the phorbol ester TPA we detected a weak expression of Met/HGF receptor specific transcripts of 9.0 kb in peripheral blood mononuclear cells of a healthy donor. Cytogenetic analyses of three of the four cell lines which express the Met/HGF receptor gene revealed structural or numerical abnormalities of the long arm of chromosome 7, where the Met/HGFR gene is located, in each of the three cell lines analyzed. In one of these cell lines (L540) the Met/HGFR gene is translocated to a marker chromosome. Southern blot and pulsed field gel electrophoresis experiments did not show any rearrangement in a region of 600 kb around the Met/HGF receptor gene excluding an activation of Met/HGFR by a TPR/Met oncogenic rearrangement as described for MNNG-HOS cells and for some gastric tumors. Our data indicate that the Met/HGFR gene is deregulated in a few cases of human leukemia, Burkitt's lymphoma and Hodgkin's disease possibly by chromosomal rearrangements resulting in an overexpression of the normal Met/HGF receptor mRNA and protein without formation of a hybrid gene.
authors.affiliation: Medizinische Klinik I, Universität Köln, F.R.G.
authors.forename: M
authors.initials: M
authors.lastname: Jücker
authors.forename: A
authors.initials: A
authors.lastname: Günther
authors.forename: G
authors.initials: G
authors.lastname: Gradl
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
authors.forename: G
authors.initials: G
authors.lastname: Krueger
authors.forename: V
authors.initials: V
authors.lastname: Diehl
authors.forename: H
authors.initials: H
authors.lastname: Tesch
mesh_terms: D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases