CHARACTERIZATION OF MOLECULAR EVENTS DURING OSTEOSARCOMA DEVELOPMENT

识别癌症高危人群是一项重要的工作 癌症分子遗传学研究的目标既是为了基因筛查 以及癌症的早期发现，从而改善治疗 结果。对发生在体细胞中的次级遗传事件的研究 在肿瘤发生过程中易患个体的细胞也可能提供 对癌症潜在机制的洞察将产生影响 关于这些人的治疗和筛查。如果继承一个 P53突变会导致许多不同肿瘤的易感性，然后 次要躯体事件的时间和性质必须决定类型 实际发生的肿瘤和发生的年龄。……的必要性 获得额外的躯体变化可以解释特定年龄和 易患肿瘤的肿瘤类型外显率的差异 个人。纯合子突变与肿瘤特异性丢失 据报道，有几个隐性基因的结构杂合性 在散发性肿瘤研究中的癌基因。同样，散发性肿瘤 被证明经历了与基因组印记的作用一致的突变 在肿瘤形成过程中。通过检查所有这些次级基因 中国人肿瘤残留等位基因的变化及亲本来源 对于易患此病的个体，我们可能会理解决定 易患肿瘤的个体发生肿瘤的时间和类型。 最后，还不知道是否所有的生发序列改变都发现了 在p53或RB1基因中，构成癌症易感突变。 开发一种功能测试来确定碱基序列的效果 这些变化将有助于评估这些序列的遗传风险。 改变。

The identification of individuals at high risk for cancer is an important goal of the molecular genetic study of cancer both for genetic screening and early detection of cancers with the resulting improvement in treatment outcome. The study of secondary genetic events that occur in the somatic cells of predisposed individuals during tumorigenesis may also provide insight into the underlying mechanisms of cancer which will have an impact on the treatment and screening of these individuals. If inheritance of a p53 mutation results in predisposition to many different tumors, then the timing and nature of the secondary somatic events must determine the type of tumor that actually occurs and the age of occurrence. The necessity of acquiring additional somatic changes may explain the age-specific and tumor-type variability of penetrance in tumors from predisposed individuals. Homozygous mutations and tumor-specific losses of constitutional heterozygosity have been reported for several recessive oncogenes in studies of sporadic tumors.As well, sporadic tumors have been shown to undergo mutations consistent with a role for genomic imprinting during tumor formation. By examining all of these secondary genetic changes and the parental origins of the retained alleles in tumors from predisposed individuals,we may understand the mechanisms which determines the timing and type of tumors that arise in the predisposed individuals. Finally, it is not known whether all germinal sequence alterations found in the p53 or RB1 genes constitute cancer predisposing mutations. Developing a functional test to determine the effect of the base sequence changes would be useful in assessing the genetic risk of these sequence changes.