OSTEO-SARCOMA AND RETINOBLASTOMA - A SHARED CHROMOSOMAL MECHANISM REVEALING RECESSIVE PREDISPOSITION
OSTEO-SARCOMA AND RETINOBLASTOMA - A SHARED CHROMOSOMAL MECHANISM REVEALING RECESSIVE PREDISPOSITION
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DOI：
10.1073/pnas.82.18.6216
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
CAVENEE, WK
中科院分区：
文献类型：
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作者：
HANSEN, MF;KOUFOS, A;CAVENEE, WK
可遗传性视网膜母细胞瘤的幸存者随后发展为第二原发性骨肉瘤，其发生率明显高于一般人群或非遗传性视网膜母细胞瘤的幸存者。在这里，我们提出的分子遗传学证据表明，这两种不同的肿瘤类型的发展涉及特定的体细胞丢失的体质杂合性的区域，包括RB1基因座的人类染色体13。类似的事件发生在非遗传性骨肉瘤的发生过程中，而不是在其他几个胚胎性肿瘤或肉瘤。这些发现表明，一个概念性的方法来确定隐性突变形式易患癌症的基因的数量是临床相关肿瘤类型的分子遗传学分析。他们还认为，混合癌家族的分子基础可能是组织特异性有丝分裂分离异常导致的单一多效性隐性突变的差异表达。
Survivors of the heritable form of retinoblastoma subsequently develop second primary osteosarcomas at substantially greater frequency than either the general population or survivors of nonheritable retinoblastoma. Here we present molecular genetic evidence that the development of these two disparate tumor types involves specific somatic loss of constitutional heterozygosity for the region of human chromosome 13 that includes the RB1 locus. Similar events occur during the genesis of nonheritable osteosarcoma but not in several other embryonal tumors or sarcomas. These findings suggest that a conceptual approach toward defining the number of genes whose recessive mutant forms predispose to cancer is the molecular genetic analysis of clinically associated tumor types. They also suggest that the molecular basis of mixed cancer families may be differential expression of a single pleiotropic recessive mutation by tissue specific mitotic segregation abnormalities.