Allelic loss from chromosome 11 in parathyroid tumors.
Allelic loss from chromosome 11 in parathyroid tumors.
复制标题
甲状旁腺肿瘤中 11 号染色体等位基因丢失。
作者：
Eitan Friedman;L. D. Marco;P. Gejman;J. A. Norton;Allen E. Bale;G. Aurbach;A. M. Spiegel;Stephen J. Marx
甲状旁腺肿瘤可能以散发的方式发生，或者更罕见地，作为家族综合征的一部分（如家族性多发性内分泌瘤I型）。MENI基因已经通过连锁分析定位于11号染色体的q11-q13带，并且推测其作为肿瘤抑制基因。在本研究中，这是我们以前的研究的延伸，我们检查了41例甲状旁腺肿瘤患者的家族性多发性内分泌腺瘤病I型和61散发性甲状旁腺肿瘤与标记物上的11号染色体，以评估这些肿瘤的等位基因丢失的程度。24例MENI相关肿瘤（58%）和16例散发性甲状旁腺肿瘤（26%）显示11号染色体等位基因丢失。MENI相关肿瘤中等位基因丢失的重叠区域使我们能够将MENI基因放置在PGA着丝粒和INT 2端粒之间，该区域跨越约7.5 cM。与通过连锁分析的位点排序一起，这清楚地将MENI基因端粒定位于PGA位点。我们无法检测到某些甲状旁腺肿瘤中11号染色体上的等位基因缺失，这表明存在其他基因参与了这一亚群可能的单克隆肿瘤的发展和/或进展;或者在某些甲状旁腺肿瘤中发生了涉及11 q肿瘤抑制基因的局部事件，这些肿瘤的检测超出了我们分析的灵敏度;或者至少一些分析的标本实际上主要是增生的甲状旁腺组织。
Parathyroid tumors may occur in a sporadic fashion or, more rarely, as part of a familial syndrome (such as familial multiple endocrine neoplasia type I). The MENI gene has been mapped by linkage analysis to chromosome 11 at band q11-q13, and presumably acts as a tumor suppressor gene. In the present study, which is an extension of our previous studies, we examined 41 parathyroid tumors from patients with familial multiple endocrine neoplasia type I and 61 sporadic parathyroid tumors with markers on chromosome 11, to assess the extent of allelic loss in those tumors. Twenty-four of the MENI-associated tumors (58%) and 16 of the sporadic parathyroid tumors (26%) displayed allelic loss from chromosome 11. The region of overlap of the allelic losses in the MENI-associated tumors enables us to place the MENI gene between PGA centromerically and INT2 telomerically, a region spanning about 7.5 cM. Taken together with locus ordering by linkage analysis, this clearly localizes the MENI gene telomeric to the PGA locus. Our inability to detect allelic loss on chromosome 11 in some parathyroid tumors suggests the existence of other genes involved in the development and/or progression of this subgroup of presumably monoclonal tumors; or that localized events involving the 11q tumor suppressor gene have occurred in some parathyroid tumors whose detection is beyond the sensitivity of our analysis; or that at least some of the specimens analyzed were in fact primarily hyperplastic parathyroid tissue.
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