Identification of novel regions of deletion in familial Wilms' tumor by comparative genomic hybridization.
Identification of novel regions of deletion in familial Wilms' tumor by comparative genomic hybridization.
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发表时间：
1996-08
期刊：
影响因子：
11.2
通讯作者：
R. Altura;M. Valentine;Hao Li;J. Boyett;P. Shearer;P. Grundy;D. Shapiro;A. Look
中科院分区：
文献类型：
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作者：
R. Altura;M. Valentine;Hao Li;J. Boyett;P. Shearer;P. Grundy;D. Shapiro;A. Look
肾母细胞瘤是一种胚胎肾肿瘤，主要诊断于幼儿，可发生在非遗传性(散发性)或家族性形式，后者出现较早，且更常发生在双侧部位。虽然家族性Wilms‘s肿瘤是通过易感肿瘤抑制基因的两个等位基因的遗传和获得性突变失活而发生的，但只有一小部分病例可以通过影响WT1基因的突变或与11号染色体短臂上的BWS区Beckwith-Weidemann综合征的连锁来解释。为了寻找可能包含与该病发生有关的重要基因的染色体区域，我们使用比较基因组杂交技术分析了来自家族性病例的肿瘤标本中持续丢失的染色体区域。虽然肿瘤抑制基因的遗传性病变通常是失活的点突变，但在恶性克隆中伴随的躯体病变通常是染色体缺失；因此，家族性肿瘤的共同缺失区域可能含有与家族易感性相关的基因。在所研究的8个家族性病例中，有广泛的基因组异常，平均每个肿瘤有6.5个改变(范围0-22)。与生物学相关的最一致的发现是4号染色体(共识，4q21-QTER)、9号染色体(共识，9p21-PTER)、20p和3号染色体(共识，3q12-q21)的缺失。这些区域以前没有涉及到Wilms‘s肿瘤，可能含有新的基因，可以帮助试图了解家族易感性以及这些肿瘤的发展和进展。
Wilms' tumor, an embryonic renal neoplasm diagnosed primarily in young children, can occur in either a noninheritable (sporadic) or a familial form, with the latter presenting earlier and more often at bilateral sites. Although familial Wilms' tumor is thought to develop through inherited and acquired mutational inactivation of the two alleles of predisposing tumor suppressor genes, only a small percentage of cases can be accounted for by mutations affecting the WT1 gene or linkage to the Beckwith-Weidemann syndrome of the BWS region on the short arm of chromosome 11. To find chromosomal regions that might contain genes important in the development of this disease, we used comparative genomic hybridization to analyze tumor specimens from familial cases for chromosomal regions that were consistently lost. Although inherited lesions of tumor suppressors are most often inactivating point mutations, accompanying somatic lesions in the malignant clones are often chromosomal deletions; therefore, consensus regions of loss in familial tumors are likely to harbor genes linked to familial predisposition. There were extensive genomic aberrations among the eight familial cases studied, with an average of 6.5 changes/tumor (range, 0-22). The most consistent findings with likely biological relevance were deletions of chromosomes 4 (consensus, 4q21-qter), 9 (consensus, 9p21-pter), 20p, and 3 (consensus, 3q12-q21). These regions have not been previously implicated in Wilms' tumor and may harbor novel genes that could aid attempts to understand the familial predisposition as well as the development and progression of these tumors.