title: Somatic in frame deletions not involving juxtamembranous cysteine residues strongly activate the RET proto-oncogene.
abstract: Somatic RET mutations have been identified in a variable proportion (about 30-70%) of sporadic Medullary Thyroid Carcinoma (MTC) cases. They are represented by the Met918Thr substitution (exon 16) typical of Multiple Endocrine Neoplasia type 2B (MEN2B) and, to a lesser extent, by nucleotide changes occurring at one of five critical cysteine residues (exons 10 and 11) typical of MEN type 2A (MEN2A). An in vitro transforming activity has already been demonstrated for these mutations. A few different MTC somatic mutations have been reported so far whose biological activity has still to be tested. In this paper we report the identification, in two MTC tumor samples, of two interstitial deletions of 48 bp and 6 bp occurred in exons 10 and 11 respectively. Both were somatic heterozygous in frame mutations, not involving any cysteine residue. Moreover, the expression of a full length RET cDNA carrying one of the two deletions demonstrated a strong transforming capacity in NIH3T3 cells.
authors.affiliation: Laboratorio di Genetica Molecolare, Istituto G. Gaslini, Genova, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.forename: B
authors.initials: B
authors.lastname: Pasini
authors.forename: F
authors.initials: F
authors.lastname: Pacini
authors.forename: M
authors.initials: M
authors.lastname: Gullo
authors.forename: I
authors.initials: I
authors.lastname: Bongarzone
authors.forename: C
authors.initials: C
authors.lastname: Romei
authors.forename: G
authors.initials: G
authors.lastname: Santamaria
authors.forename: I
authors.initials: I
authors.lastname: Matera
authors.forename: P
authors.initials: P
authors.lastname: Mondellini
authors.forename: L
authors.initials: L
authors.lastname: Scopsi
authors.forename: A
authors.initials: A
authors.lastname: Pinchera
authors.forename: M A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: G
authors.initials: G
authors.lastname: Romeo
mesh_terms: D016475:3T3 Cells; D000328:Adult; D000818:Animals; D018276:Carcinoma, Medullary / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D003545:Cysteine; D029721:Drosophila Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017384:Sequence Deletion; D013964:Thyroid Neoplasms / Q000235:genetics; D014162:Transfection
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; D003545:Cysteine