Loss of heterozygosity at 19p13.2 and 2q21 in tumours from familial clusters of non-medullary thyroid carcinoma Hugo Joa ˜o Prazeres Æ Fernando Rodrigues Æ Paula Soares Æ Plamen Naidenov Æ Paulo Figueiredo Æ Beatriz Campos Æ Manuela Lacerda Æ Teresa C. Martins Published online: 7 September 2007 Ó Springer Science + Business Media B.V. 2007 Abstract Linkage studies have identified susceptibility loci for familial nonmedullary thyroid cancer (FNMTC), with and without cell oxyphilia, at chromosomal regions 19p13.2 and 2q21. There are few genetic analyses of FNMTC tumours reported at the present time and the eventual gene involved was not identified yet. The aim of this study was to assess the occurrence of loss of hetero- zygosity (LOH) at these loci in the tumours from familial clusters of NMTC. We have analysed LOH in 14 tumours from 9 two-case familial clusters of NMTC. Using paired blood (normal) and tumour DNA samples, we have geno- typed ten microsatellite and one SNP markers throughout 19p13.2 and fourteen microsatellite markers at 2q21. Overall, eight (57%) and two (14%) out of the fourteen tumours analysed exhibited LOH at 19p13.2 and 2q21, respectively. In two families (22%), LOH for the same markers was demonstrable in the tumours of the two members of the same family. In one family (11%) LOH was demonstrable at both loci analysed. In four two-case familial clusters (44%), LOH at the 19p13.2 locus was found in only one of the tumour cases analysed. Detailed haplotype analysis showed that, in two families (22%), the pattern of LOH in tumours was consistent with selective retention of the haplotype shared by affected members. In the remaining cases, it was consistent with random allelic losses. In conclusion, we report the finding of LOH at the 19p13.2 and 2q21 loci in tumours from familial clusters of NMTC, providing evidence that inactivation of putative genes in these regions, acting as tumour-suppressors, may be involved in the development of tumours in the context of FNMTC. Keywords Familial non-medullary thyroid cancer Á Loci 19p13.2 and 2q21 Á Loss of heterozygosity Á Tumour-suppressor genes Abbreviations BL BiLateral CO Cell Oxyphilia FA Follicular Adenoma FFPE Formalin Fixed Paraffin Embedded Tissue FNMTC Familial Non-Medullary Thyroid Carcinoma FTC Follicular Thyroid Carcinoma FV Follicular Variant of Papillary Thyroid Carcinoma LOH Loss-of-heterozygosity MF MultiFocal MNG MultiNodular Goitre N Normal DNA NMTC Non-Medullary Thyroid Carcinoma H. J. Prazeres (&) Á T. C. Martins Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, Avenida Bissaya Barreto, 98, 3000-075 Coimbra, Portugal e-mail: upmolecular@croc.min-saude.pt H. J. Prazeres Á P. Soares Medical Faculty of the University of Porto, Porto, Portugal F. Rodrigues Á P. Naidenov Á B. Campos Endocrinology Service, Portuguese Institute of Oncology of Coimbra FG, EPE, Coimbra, Portugal P. Soares Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal P. Figueiredo Á M. Lacerda Laboratory of Histopathology, Portuguese Institute of Oncology of Coimbra FG, EPE, Coimbra, Portugal T. C. Martins Centre of Neurosciences of Coimbra, Coimbra, Portugal 123 Familial Cancer (2008) 7:141–149 DOI 10.1007/s10689-007-9160-x