The ret/ptc1 oncogene is activated in familial adenomatous polyposis-associated thyroid papillary carcinomas.
Familial adenomatous polyposis (FAP) is caused by germ-line mutations of the apc gene, and it is associated with an increased risk of developing papillary thyroid carcinomas. We have previously reported that a significant fraction of sporadic human papillary thyroid carcinomas is characterized by gene rearrangements affecting the ret protooncogene. These rearrangements generate chimeric transforming oncogenes designated ret/ptc. By a combined immunohistochemical and RT-PCR approach, we analyzed, for ret/ptc oncogene activation, papillary thyroid carcinomas occurred in two FAP kindreds, both showing typical apc gene mutations. Kindred 1 had seven members affected by FAP, and among these, three patients showed papillary thyroid carcinomas. Kindred 2 had two patients, mother and daughter, affected by colonic polyposis; the 20-yr-old daughter showed also a papillary carcinoma. Here we report that ret/ptc1 oncogene was activated in two of the three papillary carcinomas of FAP kindred 1 and in the papillary carcinoma of FAP kindred 2. These findings document that loss of function of apc coexists with gain of function of ret in some papillary thyroid carcinomas, suggesting that ret/ptc1 oncogene activation could be a progression step in the development of FAP-associated thyroid tumors.
Cetta
F
F
Istituto di Clinica Chirurgica, Università di Siena, Nuovo Policlinico, Italy.
Chiappetta
G
G
Melillo
R M
RM
Petracci
M
M
Montalto
G
G
Santoro
M
M
Fusco
A
A
D011125:Adenomatous Polyposis Coli / Q000150:complications*; D000328:Adult; D002291:Carcinoma, Papillary / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D009857:Oncogenes / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila