Original Paper
Oncogene (2004) 23, 8432–8438. doi:10.1038/sj.onc.1207766 Published online 20 September 2004
The tyrosine phosphatase PTPRJ/DEP-1 genotype affects thyroid carcinogenesis
Rodolfo Iuliano1, Ilaria Le Pera1, Carmela Cristofaro1, Francesco Baudi1, Franco Arturi1, PierLorenzo Pallante2, Maria Luisa Martelli1, Francesco Trapasso1, Lorenzo Chiariotti1 and Alfredo Fusco1,2
- 1Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università degli Studi di Catanzaro 'Magna Graecia', 88100 Catanzaro, Italy
- 2Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R. c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università di Napoli 'Federico II', 80131 Napoli, Italy
Correspondence: A Fusco, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università di Napoli 'Federico II', via Pansini 5, 80131 Napoli, Italy. E-mail: afusco@napoli.com
Received 2 February 2004; Revised 19 March 2004; Accepted 19 March 2004; Published online 20 September 2004.
Abstract
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.
Keywords:
polymorphisms, tyrosine phosphatase, thyroid, carcinoma, loss of heterozygosity
