CHARACTERIZATION OF MOLECULAR EVENTS DURING OSTEOSARCOMA DEVELOPMENT

识别癌症高危人群是一项重要的 癌症分子遗传学研究的目标是进行遗传筛查， 以及癌症的早期发现，从而改善治疗 结果。体细胞遗传学对发生在体细胞中的次生遗传事件的研究 在肿瘤发生过程中，易感个体的细胞也可以提供 深入了解癌症的潜在机制， 对这些人的治疗和筛查。如果继承一个 p53突变导致易患多种不同肿瘤， 次级躯体事件的时间和性质必须决定 肿瘤的发生率和发病年龄。的必要性 获得额外的躯体变化可以解释年龄特异性， 易患肿瘤的肿瘤类型变异性 个体纯合子突变和肿瘤特异性缺失 已报道了几种隐性遗传 在散发性肿瘤的研究中， 显示发生了与基因组印记作用一致的突变 在肿瘤形成过程中。通过检查所有这些次级遗传 肿瘤中保留等位基因的变化和亲本来源， 我们可以理解决定这些人的机制 在易感个体中出现肿瘤的时间和类型。 最后，尚不清楚是否所有的germ序列改变都被发现， 在p53或RB1基因构成癌症易感突变。 开发功能测试以确定碱基序列的影响 改变将有助于评估这些序列的遗传风险 变化

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.