A complex pattern of mutations and abnormal splicing of Smad4 is present in thyroid tumours

Davide Lazzereschi, Francesco Nardi, Alessandra Turco, Laura Ottini, Cristina D'Amico, Renato Mariani-Costantini, Alberto Gulino, Anna Coppa

Research output: Contribution to journalArticlepeer-review


Sensitivity to transforming growth factor-β is impaired in thyroid tumours. Similar to Mad - Mother Against Decapentaplegic-(Smad)4 is frequently altered in cancers, but its involvement in this system is unknown. We analysed 56 thyroid tumours of various histotypes for Smad4 mutations by PCR-SSCP and sequencing, linking them to Smad4 reactivity as examined by immunohistochemistry (IHC), and 29 of them also for abnormalities in RNA expression due to alternative splicing. In all, 15/56 cases (27%), both benign and malignant lesions, harbour alterations of Smad4 coding sequence. We found several novel intragenic mutations (13 missense, two silent, one frameshift and one large insertion-deletion), with high incidence in the linker region. A subset of mutated tumours failed to express Smad4 protein by IHC. We have also detected four alternatively spliced tumour-associated Smad4 isoforms, lacking portions of the linker region, and three more due to unreported internal exon-exon rearrangements. Smad4 is both frequently mutated and deregulated by aberrant splicing in thyroid tumours and these alterations may contribute as an early event to thyroid tumorigenesis.

Original languageEnglish
Pages (from-to)5344-5354
Number of pages11
Issue number34
Publication statusPublished - Aug 11 2005


  • Abnormal splicing
  • Molecular pathology
  • Smad4
  • Somatic mutations
  • TGF-β signalling
  • Thyroid tumours

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics


Dive into the research topics of 'A complex pattern of mutations and abnormal splicing of Smad4 is present in thyroid tumours'. Together they form a unique fingerprint.

Cite this