Allelic imbalances in human bladder cancer: genome-wide detection with high-density single-nucleotide polymorphism arrays.
Allelic imbalances in human bladder cancer: genome-wide detection with high-density single-nucleotide polymorphism arrays.
复制标题
人类膀胱癌的等位基因失衡：利用高密度单核苷酸多态性阵列进行全基因组检测。
DOI：
10.1093/jnci/94.3.216
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
T. Orntoft
中科院分区：
文献类型：
--
作者：
H. Primdahl;F. Wikman;H. von der Maase;Xiaoqing Zhou;H. Wolf;T. Orntoft
背景
膀胱癌的特征在于基因组不稳定性。在这项研究中，我们调查了是否使用单核苷酸多态性（SNP）阵列的全基因组筛查可以检测等位基因不平衡（至少一个等位基因的丢失或获得）在膀胱癌。
方法
对于微阵列分析，从来自11名患者的显微切割的膀胱肿瘤和白细胞中分离DNA。T1期肿瘤（结缔组织浸润性）和随后的T2-4期肿瘤（肌肉浸润性）可从这些患者中的8例获得，只有第一个肌肉浸润性T2-4期肿瘤可从11例患者中的3例获得。微阵列包含1494个双等位基因多态性序列。对于微卫星分析，从9名原发性T2-4肿瘤患者和13名Ta（非侵袭性）肿瘤患者的肿瘤和白细胞中分离DNA。所有统计检验均为双侧检验。
结果
我们分配了1204个位点的基因型，其中343个是杂合子。在6、8、9、11和17号染色体上已知的不平衡区域检测到等位基因不平衡，在6号染色体的p臂上检测到一个新的不平衡区域。对其他9个T2-4肿瘤和13个Ta肿瘤的微卫星分析表明，等位基因失衡在T2-4肿瘤中比Ta肿瘤更常见（P<0.001）。我们在T1肿瘤的348个信息位点中检测到8.5个等位基因不平衡（中位数），在T2-4肿瘤的329个信息位点中检测到28个等位基因不平衡（中位数）。当对来自8名患者的T1和T2-4肿瘤进行分析时，在T1肿瘤中检测到的68%的不平衡（146个不平衡）发生在随后的T2-4肿瘤中（99个不平衡）。纯合子TP 53突变与高等位基因失衡的相关性（P = 0.005）高于与低等位基因失衡的相关性。
结论
单核苷酸多态性阵列是可行的高通量，全基因组扫描等位基因失衡的膀胱癌。
BACKGROUND
Bladder cancer is characterized by genomic instability. In this study, we investigated whether genome-wide screening using single-nucleotide polymorphism (SNP) arrays could detect allelic imbalance (loss or gain of at least one allele) in bladder cancers.
METHODS
For microarray analysis, DNA was isolated from microdissected bladder tumors and leukocytes from 11 patients. The stage T1 tumor (connective tissue invasive) and the subsequent stage T2-4 tumor (muscle invasive) were available from eight of these patients, and only the first muscle-invasive stage T2-4 tumor was available from three of the 11 patients. The microarray contained 1494 biallelic polymorphic sequences. For microsatellite analyses, DNA was isolated from tumors and leukocytes of nine patients with primary T2-4 tumors and 13 patients with Ta (noninvasive) tumors. All statistical tests were two-sided.
RESULTS
We assigned a genotype to 1204 loci, 343 of which were heterozygous. Allelic imbalance was detected in known areas of imbalance on chromosomes 6, 8, 9, 11, and 17, and a new area of imbalance was detected on the p arm of chromosome 6. Microsatellite analysis of nine other T2-4 tumors and 13 Ta tumors showed that allelic imbalance was more frequent in T2-4 tumors than in Ta tumors (P<.001). We detected 8.5 allelic imbalances (median) in 348 informative loci in T1 tumors and 28 allelic imbalances (median) in 329 informative loci in T2-4 tumors. When pairs of T1 and T2-4 tumors were analyzed from eight patients, 68% of imbalances detected in T1 tumors (146 imbalances) occurred in the subsequent T2-4 tumors (99 imbalances). Homozygous TP53 mutations were more often associated (P =.005) with high allelic imbalance than with low allelic imbalance.
CONCLUSION
SNP arrays are feasible for high-throughput, genome-wide scanning for allelic imbalances in bladder cancer.
影响因子：
30.8
作者：
Marth, G;Yeh, R;Kwok, PY
通讯作者：
Kwok, PY