CLONAL ORIGIN OF BLADDER-CANCER
CLONAL ORIGIN OF BLADDER-CANCER
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DOI：
10.1056/nejm199203123261104
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发表时间：
1992-03-12
影响因子：
158.5
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
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作者：
SIDRANSKY, D;FROST, P;VOGELSTEIN, B
背景膀胱癌患者通常会出现多个肿瘤，出现在不同的时间和膀胱的不同部位。这一观察结果归因于膀胱中的“场缺陷”，其允许上皮细胞在多个位点独立转化。我们测试了这一假设，使用分子遗传技术。我们使用一种分析X染色体失活模式的方法，检查了来自4名妇女的13个cybergene标本中的肿瘤，以确定肿瘤是否来源于相同的前体细胞。此外，我们分析了常染色体上的等位基因丢失，以确定不同的肿瘤是否具有相同的遗传改变。评估的改变包括染色体9q序列的丢失（常见于浅表性膀胱肿瘤）和17p和18q序列的丢失（通常仅见于晚期肿瘤）。对于每一个研究的病人，所有的肿瘤都有相同的X染色体失活，而正常的膀胱粘膜细胞有随机的失活模式。此外，可以从给定患者中评估的每个肿瘤都丢失了染色体9q上的相同等位基因，这表明该等位基因的丢失先于肿瘤细胞在膀胱其他部位的扩散。染色体17p和18q等位基因的丢失是肿瘤进展的晚期事件，在同一患者的不同肿瘤中并不常见。许多膀胱肿瘤可由单个转化细胞的不受控制的扩散引起。然后，这些肿瘤可以独立生长，随后发生可变的遗传改变。
Background. Patients with cancer of the urinary bladder often present with multiple tumors, appearing at different times and at different sites in the bladder. This observation has been attributed to a "field defect" in the bladder that allows the independent transformation of epithelial cells at a number of sites. We tested this hypothesis using molecular genetic techniques.Methods. We examined 13 tumors from cystectomy specimens from four women, using a method that analyzes the pattern of X-chromosome inactivation to determine whether the tumors were derived from the same precursor cell. In addition, we analyzed allelic loss on autosomes to determine whether different tumors had the same genetic alterations. The alterations evaluated included the loss of chromosome 9q sequences (commonly found in superficial bladder tumors) and the loss of 17p and 18q sequences (usually found only in advanced tumors).Results. For each patient studied, all the tumors had inactivation of the same X chromosome, whereas normal bladder mucosa cells had random patterns of inactivation. Moreover, each tumor that could be evaluated from a given patient had lost the same allele on chromosome 9q, suggesting that the loss of this allele preceded the spread of neoplastic cells elsewhere in the bladder. The losses of chromosome 17p and 18q alleles, which are late events in tumor progression, were not common to different tumors from the same patient.Conclusions. A number of bladder tumors can arise from the uncontrolled spread of a single transformed cell. These tumors can then grow independently with variable subsequent genetic alterations.