Abstract for presentation at 11th International Congress of Human Genetics

Familial Thyroid Tumors: mutation analysis of candidate genes mapping to chromosome 19p13.2 genes and their relevance for the oncocytic phenotype

  • Dr Elena Bonora, Unit of Medical Genetics-Dept of Internal medicine University of Bologna, Italy
  • Ms Cecilia Evangelisti, t of Medical Genetics-Dept of Internal medicine University of Bologna, Italy
  • Mr Giuseppe Gasparre, t of Medical Genetics-Dept of Internal medicine University of Bologna, Italy
  • Prof Giovanni Romeo, t of Medical Genetics-Dept of Internal medicine University of Bologna, Italy

    • NMTC (Non-Medullary Thyroid Carcinoma) includes three different types of neoplasia: papillary, follicular and undifferentiated forms and accounts for 80-90% of all thyroid neoplasias. Familial NMTC (fNMTC) represents 3-7% of all thyroid tumors and is associated with some of the highest familial recurrence among all cancers. Tumors are multifocal, recur more frequently, and show an earlier age of onset than sporadic cases. Inheritance patterns indicate that fNMTC is transmitted as an autosomal dominant trait with reduced penetrance, but a multigenic inheritance could not be excluded.
    TCO (Thyroid Carcinoma with cell Oxyphilia), a predisposing locus for recurrence of oncocytic (oxyphilic) thyroid tumors, was previously mapped to the 19p13.2 region in a large French family. Oncocytic adenomas and carcinomas are a subset of thyroid tumors predominantly composed (at least 75%) of oncocytic cells. These cells are characterized by an aberrant accumulation of mitochondria that results in a distinctive granular eosinophilic appearance. From a clinical standpoint, the overall mortality rate of oncocytic carcinoma appears to be considerably higher than that of non-oncocytic thyroid tumors. The increased mortality risk is likely due to decreased competence in iodine uptake by the tumor cells and the consequent reduced responsiveness to radioiodine treatment.
    Results from linkage studies in additional families with the TCO phenotype led us to refine the TCO region on chr19 to a 1.6 Mb interval. In order to identify the TCO predisposing variant(s), genes mapping to chromosome 19p13.2 and encoding for proteins involved in mitochondrial pathways or in tumor development have been analyzed in the affected individuals from the families contributing to the linkage peak. The screening was focused to the coding and regulatory regions of genes mapping to the region of interest. Twenty genes have been studied so far and results will be presented.

    Conference Organiser - ICMS Pty Ltd