Canzian F, Amati P, Harach H R, Kraimps J L, Lesueur F, Barbier J, Levillain P, Romeo G, Bonneau D
Unit of Genetic Cancer Susceptibility, International Agency for Research on Cancer, Lyon, France.
Am J Hum Genet. 1998 Dec;63(6):1743-8. doi: 10.1086/302164.
Familial nonmedullary thyroid cancer (FNMTC) is a clinical entity characterized by a phenotype more aggressive than that of its sporadic counterpart. Families with recurrence of nonmedullary thyroid cancer (NMTC) have been repeatedly reported in the literature, and epidemiological data show a very high relative risk for first-degree relatives of probands with thyroid cancer. The transmission of susceptibility to FNMTC is compatible with autosomal dominant inheritance with reduced penetrance, or with complex inheritance. Cases of benign thyroid disease are often found in FNMTC kindreds. We report both the identification of a new entity of FNMTC and the mapping of the responsible gene, named "TCO" (thyroid tumors with cell oxyphilia), in a French pedigree with multiple cases of multinodular goiter and NMTC. TCO was mapped to chromosome 19p13.2 by linkage analysis with a whole-genome panel of microsatellite markers. Interestingly, both the benign and malignant thyroid tumors in this family exhibit some extent of cell oxyphilia, which, until now, had not been described in the FNMTC. These findings suggest that the relatives of patients affected with sporadic NMTC with cell oxyphilia should be carefully investigated.
家族性非髓样甲状腺癌（FNMTC）是一种临床实体，其表型比散发性非髓样甲状腺癌更具侵袭性。文献中多次报道了非髓样甲状腺癌（NMTC）复发的家族，流行病学数据显示，甲状腺癌先证者的一级亲属具有非常高的相对风险。FNMTC易感性的传递符合外显率降低的常染色体显性遗传，或符合复杂遗传。在FNMTC家族中常发现良性甲状腺疾病病例。我们报告了在一个有多个多结节性甲状腺肿和NMTC病例的法国家系中，鉴定出一种新的FNMTC实体并对其致病基因进行定位，该基因名为“TCO”（嗜酸性细胞性甲状腺肿瘤）。通过与全基因组微卫星标记物面板进行连锁分析，将TCO定位到19号染色体p13.2区域。有趣的是，该家族中的良性和恶性甲状腺肿瘤均表现出一定程度的细胞嗜酸性，而迄今为止，这在FNMTC中尚未见报道。这些发现表明，对于散发性有细胞嗜酸性的NMTC患者的亲属应进行仔细调查。
