Nord B, Larsson C, Wong F K, Wallin G, Teh B T, Zedenius J
Endocrine Tumor Unit, Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Genes Chromosomes Cancer. 1999 Sep;26(1):35-9. doi: 10.1002/(sici)1098-2264(199909)26:1<35::aid-gcc5>3.0.co;2-l.
Loss of heterozygosity (LOH) in 11q13 where the tumor suppressor gene for multiple endocrine neoplasia type 1 (MEN 1) is located has been demonstrated in several tumor types, including follicular thyroid tumors, but whether the MEN1 gene is actually involved in their tumorigenesis is not known. In the present study, the involvement of the MEN1 gene in follicular thyroid tumors was investigated. By using 14 MEN1-linked microsatellite markers, LOH was demonstrated in 12 out of 60 follicular thyroid tumors: 2/18 adenomas, 4/15 atypical adenomas, 1/6 Hürthle cell adenomas, 1/9 carcinomas, 3/6 Hürthle cell carcinomas, and 1/6 anaplastic carcinomas. In the tumors with LOH, a single minimal region of overlapping deletions was mapped to the 200-kb interval between D11S4946 and D11S4939. Tumors that showed 11q13 LOH were screened for mutations of the MEN1 gene using single-strand conformation analysis. Abnormal shifts detected in seven tumors in two exons were sequenced, which revealed two different polymorphisms present in both tumor and constitutional DNA, but without somatic mutation. Taken together, these results suggest that in this region, a tumor suppressor gene other than MEN1 might be involved in the tumorigenesis of follicular thyroid tumors. Genes Chromosomes Cancer 26:35-39, 1999.
11号染色体长臂13区（11q13）是多发性内分泌腺瘤1型（MEN 1）肿瘤抑制基因所在区域，在包括甲状腺滤泡性肿瘤在内的多种肿瘤类型中已证实存在杂合性缺失（LOH），但MEN1基因是否实际参与其肿瘤发生尚不清楚。在本研究中，对MEN1基因在甲状腺滤泡性肿瘤中的作用进行了研究。通过使用14个与MEN1连锁的微卫星标记，在60例甲状腺滤泡性肿瘤中的12例中检测到LOH：18例腺瘤中有2例，15例非典型腺瘤中有4例，6例许特耳细胞腺瘤中有1例，9例癌中有1例，6例许特耳细胞癌中有3例，6例间变性癌中有1例。在发生LOH的肿瘤中，单个最小重叠缺失区域定位于D11S4946和D11S4939之间的200 kb区间。对显示11q13 LOH的肿瘤使用单链构象分析筛查MEN1基因突变。对两个外显子中七个肿瘤检测到的异常迁移进行测序，结果显示肿瘤和正常组织DNA中均存在两种不同的多态性，但无体细胞突变。综上所述，这些结果表明在该区域，可能有除MEN1之外的肿瘤抑制基因参与甲状腺滤泡性肿瘤的发生。《基因、染色体与癌症》26:35 - 39，1999年。
