Prazeres Hugo João, Rodrigues Fernando, Soares Paula, Naidenov Plamen, Figueiredo Paulo, Campos Beatriz, Lacerda Manuela, Martins Teresa C
Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, Avenida Bissaya Barreto, 98, 3000-075, Coimbra, Portugal.
Fam Cancer. 2008;7(2):141-9. doi: 10.1007/s10689-007-9160-x. Epub 2007 Sep 7.
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 heterozygosity (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 genotyped 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.
连锁研究已经确定了19p13.2和2q21染色体区域是伴有或不伴有嗜酸性细胞的家族性非髓样甲状腺癌（FNMTC）的易感基因座。目前报道的关于FNMTC肿瘤的基因分析很少，且尚未确定最终涉及的基因。本研究的目的是评估这些基因座在NMTC家族聚集性肿瘤中的杂合性缺失（LOH）情况。我们分析了来自9个NMTC双病例家族聚集性病例的14个肿瘤中的LOH。使用配对的血液（正常）和肿瘤DNA样本，我们对整个19p13.2区域的10个微卫星和1个单核苷酸多态性（SNP）标记以及2q21区域的14个微卫星标记进行了基因分型。总体而言，在分析的14个肿瘤中，分别有8个（57%）和2个（14%）在19p13.2和2q21处出现了LOH。在两个家族（22%）中，同一家族两名成员的肿瘤中可检测到相同标记的LOH。在一个家族（11%）中，在两个分析的基因座处均检测到LOH。在4个双病例家族聚集性病例（44%）中，仅在其中一个分析的肿瘤病例中发现了19p13.2基因座处的LOH。详细的单倍型分析表明，在两个家族（22%）中，肿瘤中LOH的模式与受影响成员共享的单倍型的选择性保留一致。在其余病例中，与随机等位基因缺失一致。总之，我们报告了在NMTC家族聚集性肿瘤中19p13.2和2q21基因座处存在LOH的发现，这为这些区域中作为肿瘤抑制因子的假定基因失活可能参与FNMTC背景下肿瘤的发生提供了证据。
