Frequent activation of ret protooncogene by fusion with a new activating gene in papillary thyroid carcinomas

I. Bongarzone, M. G. Butti, S. Coronelli, M. G. Borrello, M. Santoro, P. Mondellini, S. Pilotti, A. Fusco, G. Della Porta

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor specific rearrangements of ret gene are frequently detected in papillary thyroid carcinomas. These rearrangements result in the formation of chimeric genes showing the tyrosine kinase domain of ret fused with the 5' end sequences of different genes. We examined a series of 52 patients and identified 10 cases of ret fusion with D10S170 locus resulting in the generation of ret/PTC1 oncogene, 2 cases with the gene encoding the regulatory subunit R1α of PKA (ret/PTC2), and finally 6 cases, here described, with a newly discovered gene called ele1 localized on chromosome 10 and leading to the formation of ret/PTC3 oncogene. Our results show the expression of the ret/PTC3 hybrid gene in all the 6 cases and demonstrated its association with the synthesis of 2 constitutively phosphorylated isoforms of the oncoprotein (p75 and p80). The chromosome 10 localization of both ret and ele1 and the detection, in all cases, of a sequence reciprocal to that generating the oncogenic rearrangements, strongly suggest that ret/PTC3 formation is a consequence of an intrachromosomal inversion of chromosome 10.

Original languageEnglish
Pages (from-to)2979-2985
Number of pages7
JournalCancer Research
Volume54
Issue number11
Publication statusPublished - Jun 1 1994

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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