CLONALITY OF PARATHYROID TUMORS IN FAMILIAL MULTIPLE ENDOCRINE NEOPLASIA TYPE-1
CLONALITY OF PARATHYROID TUMORS IN FAMILIAL MULTIPLE ENDOCRINE NEOPLASIA TYPE-1
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DOI：
10.1056/nejm198907273210402
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发表时间：
1989-07-27
影响因子：
158.5
通讯作者：
MARX, SJ
中科院分区：
文献类型：
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作者：
FRIEDMAN, E;SAKAGUCHI, K;MARX, SJ
家族性多发性内分泌瘤1型（MEN-1）的特征是甲状旁腺、内分泌胰腺和垂体前叶的肿瘤。由于位于11号染色体（11 q13）上的与MEN-1相关的基因通常可以抑制肿瘤增殖，因此肿瘤可能是由于一个或两个等位基因的失活而引起的。然而，MEN-1患者的甲状旁腺肿瘤被认为是多克隆增生的结果。我们使用基因探针检测甲状旁腺肿瘤的单克隆成分，表现为11号染色体上沿着8个位点中任何一个位点的等位基因缺失。来自14名家族性MEN-1患者的16个肿瘤中有10个缺失11号染色体的等位基因。有损失的肿瘤比没有损失的肿瘤大（1.6比0.2 g; P<0.002），表明单克隆腺瘤可能在多克隆增生阶段后发展。在10个肿瘤中的7个中，丢失的子区域小于11号染色体的全长，但总是包括MEN-1基因座的一个拷贝。在34例散发性腺瘤患者没有MEN-1，9个表现出类似的等位基因损失在11号染色体，在7个损失包括明显的MEN-1 locus.We的结论，许多“增生性”甲状旁腺肿瘤家族MEN-1实际上是单克隆的，并可能进展，甚至开始发展的MEN-1基因（在11 - 13）在前体细胞的失活。一些散发性腺瘤在11号染色体上有等位基因丢失，这也可能涉及MEN-1基因。（N Engl J Med 1989; 321：213-8.）
Familial multiple endocrine neoplasia type 1 (MEN-1) is characterized by tumors of the parathyroids, endocrine pancreas, and anterior pituitary. Since the gene associated with MEN-1, located on chromosome 11 (11q13), may normally inhibit tumor proliferation, tumors could arise from inactivation of one or both of the alleles. However, parathyroid tumors in patients with MEN-1 have been considered to result from polyclonal hyperplasia. Using genetic probes, we tested parathyroid tumors for a monoclonal component, represented by a loss of alleles at any of eight loci along chromosome 11.Ten of 16 tumors from 14 patients with familial MEN-1 had losses of alleles from chromosome 11. Tumors with losses were larger than those without (1.6 vs. 0.2 g; P<0.002), suggesting that a monoclonal adenoma may develop after a phase of polyclonal hyperplasia. In 7 of 10 tumors, the subregion of loss was less than the full length of chromosome 11 but always included one copy of the MEN-1 locus. Of 34 sporadic adenomas from patients without MEN-1, 9 showed similar allelic losses in chromosome 11; in 7 the losses included the apparent MEN-1 locus.We conclude that many "hyperplastic" parathyroid tumors in familial MEN-1 are in fact monoclonal and may progress or even begin to develop by inactivation of the MEN-1 gene (at 11ϥ13) in a precursor cell. Some sporadic adenomas have allelic losses on chromosome 11, which may also involve the MEN-1 gene. (N Engl J Med 1989; 321:213–8.)