Schubert E L, Strong L C, Hansen M F
Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Hum Genet. 1997 Oct;100(5-6):557-63. doi: 10.1007/s004390050551.
The pediatric eye-tumor retinoblastoma is widely held as a paradigm of human cancer genetics and has been a model system for both the two-hit hypothesis of dominantly inherited cancer as well as for the concept of tumor-specific loss of constitutional heterozygosity to achieve expression of the tumorigenic phenotype. Familial retinoblastoma is usually inherited as an autosomal dominant disease with high penetrance and expressivity. In a small but significant number of families, however, retinoblastoma is inherited with greatly reduced penetrance and expressivity. In these families, retinoblastoma tumors occur relatively late, are often unilateral, and unaffected carriers may exist. We have identified a mutation in such a family that exhibited extremely low penetrance and expressivity. This mutation appeared to affect splicing of the mutant allele such that both a normal length RB1 mRNA and a truncated RB1 mRNA were expressed from the same allele.
小儿眼肿瘤视网膜母细胞瘤被广泛视为人类癌症遗传学的范例，并且一直是显性遗传癌症的双打击假说以及肿瘤特异性体质杂合性丧失以实现致瘤表型表达这一概念的模型系统。家族性视网膜母细胞瘤通常作为一种具有高外显率和表达度的常染色体显性疾病遗传。然而，在少数但数量可观的家族中，视网膜母细胞瘤的遗传外显率和表达度大幅降低。在这些家族中，视网膜母细胞瘤肿瘤出现相对较晚，通常为单侧性，并且可能存在未受影响的携带者。我们在这样一个具有极低外显率和表达度的家族中鉴定出了一种突变。这种突变似乎影响了突变等位基因的剪接，以至于从同一个等位基因中既表达出了正常长度的RB1 mRNA，也表达出了截短的RB1 mRNA。
