Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33
Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33
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DOI：
10.1086/321982
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发表时间：
2001-08-01
影响因子：
9.8
通讯作者：
Parry, DM
中科院分区：
文献类型：
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作者：
Kelley, MJ;Korczak, JF;Parry, DM
脊索瘤是一种罕见的肿瘤起源于脊索残余，通常是在中年诊断。我们进行了一个全基因组连锁分析，在一个家庭与10个人受脉络膜。仅基于受影响个体的最大两点LOD得分为2.21，重组分数为0，位于染色体7 q上的标记D 7S 2195处。这个家庭的其他成员（11个受影响的个人）和两个无关的家庭（一个有2个受影响的个人和其他3个受影响的个人），与20个标记在7 q的组合分析，显示了最大的两点LOD得分为4.05标记D 7S 500。仅基于受影响个体的多点分析得出的最大LOD评分为4.78，从标记D 7S 512到标记D 7S 684的支持间隔约为2-LOD。单倍型分析表明，D 7S 512 ~ D 7S 684之间存在一个最小的致病基因区域，距离为11.1cM，近似于7.1Mb。在来自受影响家族成员的四个肿瘤样本中，在标记D 7S 1804、D 7S 1824和D 7S 2195处未发现杂合性丢失。这些结果将家族性脊索瘤的基因座映射到7 q33。目前正在对该区域进行进一步分析，以确定该基因。
Chordoma is a rare tumor originating from notochordal remnants that is usually diagnosed during midlife. We performed a genomewide analysis for linkage in a family with 10 individuals affected by chordoma. The maximum two-point LOD score based on only the affected individuals was 2.21, at recombination fraction 0, at marker D7S2195 on chromosome 7q. Combined analysis of additional members of this family (11 affected individuals) and of two unrelated families (one with 2 affected individuals and the other with 3 affected individuals), with 20 markers on 7q, showed a maximum two-point LOD score of 4.05 at marker D7S500. Multipoint analysis based on only the affected individuals gave a maximum LOD score of 4.78, with an approximate 2-LOD support interval from marker D7S512 to marker D7S684. Haplotype analysis of the three families showed a minimal disease-gene region from D7S512 to D7S684, a distance of 11.1 cM and similar to7.1 Mb. No loss of heterozygosity was found at markers D7S1804, D7S1824, and D7S2195 in four tumor samples from affected family members. These results map a locus for familial chordoma to 7q33. Further analysis of this region, to identify this gene, is ongoing.