Molecular karyotype of sporadic unilateral retinoblastoma tumors.
Molecular karyotype of sporadic unilateral retinoblastoma tumors.
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散发性单侧视网膜母细胞瘤的分子核型。
DOI：
10.1097/iae.0b013e3181a0be05
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Shields,Carol
中科院分区：
文献类型：
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作者：
Ganguly,Arupa;Nichols,KimE;Grant,Gregory;Rappaport,Eric;Shields,Carol
背景：视网膜母细胞瘤（RB）是一种与肿瘤易感基因 RB1 突变相关的儿童眼部恶性肿瘤。视网膜细胞中 RB1 基因的两个拷贝失活后，会连续获得额外的遗传变化，这些变化定义了肿瘤形成的过程。方法：为了识别与 RB1 基因功能丧失相关的遗传事件，我们进行了基于单核苷酸多态性基因分型的全基因组采样测定。我们使用从 25 个散发性单侧 RB 肿瘤和匹配的血液样本中分离出的 DNA。 结果：分析基因组图谱以识别杂合性丢失或扩增的区域。 RB 肿瘤的两个主要亚类通过 13 号染色体杂合性丢失的存在（n=18）或不存在（n=7）来定义。在大多数情况下，杂合性丢失是由有丝分裂重组和有丝分裂不分离引起的复制中性事件的结果。肿瘤在 1q44、3p25、11q14、11q25、14q23、15q21、16p13、17p11 处存在新的扩增区域。 2、19q13 和 20q13，而丢失区域包括 6q22、7q21 和 21q2。结论：基于全基因组采样分析的单侧 RB 肿瘤显示新区域具有重要意义。这些丢失或扩增的最小关键区域预计含有有助于肿瘤发生过程的基因。
Background:Retinoblastoma (RB) is a childhood ocular malignancy associated with mutations in RB1, a tumor susceptibility gene. Inactivation of both copies of the RB1 gene in a retinal cell is followed by the sequential acquisition of additional genetic changes that define the course to tumor formation.Methods:To identify the genetic events that cooperate with loss of the RB1 gene function, we performed a whole genome sampling assay based on single nucleotide polymorphism genotyping. We used DNA isolated from 25 sporadic, unilateral RB tumors and matched blood samples.Results:Genomic profiles were analyzed to identify regions of loss of heterozygosity or amplification. Two major subclasses of RB tumors were defined by the presence (n= 18) or absence (n= 7) of loss of heterozygosity of chromosome 13. Loss of heterozygosity in most cases was the result of copy-neutral events caused by mitotic recombination and mitotic nondisjunction. Tumors harbored novel regions of amplification at 1q44, 3p25, 11q14, 11q25, 14q23, 15q21, 16p13, 17p11. 2, 19q13, and 20q13, whereas regions of loss included 6q22, 7q21, and 21q2.Conclusion:Whole genome sampling assay-based analysis of unilateral RB tumors revealed novel regions as significant. These minimum critical regions that are lost or amplified are expected to harbor genes that aid the process of tumorigenesis.