The tyrosine phosphatase PTPRJ/DEP-1 genotype affects thyroid carcinogenesis.
We recently isolated the r-PTPeta gene, which encodes a receptor-type tyrosine phosphatase protein that suppresses the neoplastic phenotype of retrovirally transformed rat thyroid cells. The human homologue gene PTPRJ/DEP-1 is deleted in various tumors. Moreover, the Gln276Pro polymorphism, located in the extracellular region of the gene, seems to play a critical role in susceptibility to some human neoplasias. Here we report the loss of heterozygosity (LOH) of PTPRJ in 11/76 (14.5%) informative thyroid tumors (including adenomas and carcinomas). We also looked for the Gln276Pro, Arg326Gln and Asp872Glu polymorphisms in exons 5, 6 and 13 of PTPRJ in 88 patients with thyroid tumors and in 54 healthy individuals. We found that the PTPRJ genotypes homozygous for the Gln276Pro and Arg326Gln polymorphisms, and the Asp872 allele were more frequent in thyroid carcinoma patients than in healthy individuals (P=0.032). In addition, PTPRJ LOH was more frequent in thyroid carcinomas of heterozygotes for Gln276Pro and Arg326Gln compared with homozygotes (P=0.006). This suggests that the presence of hemizygosity for these polymorphisms in the tumor facilitates tumor progression. These results indicate that the genotypic profile of PTPRJ affects susceptibility to thyroid carcinomas, and that allelic loss of this gene is involved in thyroid carcinogenesis.
Iuliano
Rodolfo
R
Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università degli Studi di Catanzaro Magna Graecia, 88100 Catanzaro, Italy.
Le Pera
Ilaria
I
Cristofaro
Carmela
C
Baudi
Francesco
F
Arturi
Franco
F
Pallante
Pierlorenzo
P
Martelli
Maria Luisa
ML
Trapasso
Francesco
F
Chiariotti
Lorenzo
L
Fusco
Alfredo
A
D000236:Adenoma / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D011110:Polymorphism, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
D005819:Genetic Markers; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3