Loss of heterozygosity at the RET protooncogene locus in a case of multiple endocrine neoplasia type 2A

Loredana Quadro, Olimpia Fattoruso, Maria Pia Cosma, Uberta Verga, Antonio Porcellini, Alfonso Libroia, Vittorio Colantuoni

Research output: Contribution to journalArticle


We describe a patient affected by multiple endocrine neoplasia type 2A (MEN 2A) bearing a heterozygous germline mutation (Cys634Arg) in exon 11 and an additional somatic mutation of the RET protooncogene. A large intragenic deletion, spanning exon 4 to exon 16, affected the normal allele and was detected by quantitative PCR, Southern blot analysis, and screening of several polymorphic markers. This deletion causes RET loss of heterozygosity exclusively in the metastasis, thus suggesting a role for this second mutational event in tumor progression. No additional mutations were found in the other exons analyzed. We provide the first evidence that RET, a dominant oncogene, is affected by a germline mutation and by an additional somatic deletion of the wild-type allele. This unusual genetic profile may be related to the clinical course and very poor outcome.

Original languageEnglish
Pages (from-to)239-244
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
Publication statusPublished - 2001


ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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