Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected by interphase cytogenetics:: basic findings and clinical aspects

Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected by interphase cytogenetics:: basic findings and clinical aspects
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DOI:
10.1038/bjc.1998.223
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发表时间:
1998-04-01
影响因子:
8.8
通讯作者:
Drach, J
Drach, J
中科院分区:
医学1区
文献类型:
--
作者:
Zojer, N;Fiegl, M;Drach, J

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到目前为止,胰腺癌的细胞遗传学研究是罕见的,并知之甚少的细胞遗传学畸变的频率在原发癌相比,转移性肿瘤细胞。因此,我们评估了染色体畸变的频率在12个原发性胰腺癌和渗出液标本25例胰腺癌患者通过使用间期荧光原位杂交(FISH)和面板的四个着丝粒探针。超二倍体和染色体不平衡,主要影响8号染色体,是一个恒定的发现在转移性渗出细胞,而一致的增益染色体或相对损失的18号染色体的特征原发性胰腺癌。通过用8q24(MYC)探针和8号染色体着丝粒探针对非整倍体渗出细胞进行双杂交研究,进一步研究了位于8号染色体上的癌基因在胰腺癌进展中的潜在作用,结果表明10例中有2例(20%)MYC癌基因扩增。最后,一个潜在的应用程序的基本调查结果在临床环境中进行了测试,通过寻找微转移细胞从胰腺癌患者的渗出液主要是阴性的FISH。双色FISH结合广泛筛查(>10 000个细胞核)似乎是一种有用的工具,通过证明超二倍体和核内染色体异质性来明确识别微转移细胞。
To date, cytogenetic studies on pancreatic carcinoma are rare, and little is known about the frequency of cytogenetic aberrations in primary carcinomas compared with metastatic tumour cells. We therefore evaluated the frequency of chromosomal aberrations in 12 primary pancreatic carcinomas and in effusion specimens from 25 patients with pancreatic cancer by using interphase fluorescence in situ hybridization (FISH) and a panel of four centromeric probes. Hyperdiploidy and chromosomal imbalances, predominantly affecting chromosome 8, were a constant finding in metastatic effusion cells, whereas concordant gain of chromosomes or relative loss of chromosome 18 characterized primary pancreatic carcinomas. The potential role of oncogenes located on chromosome 8 for pancreatic cancer progression was further investigated by double-hybridization studies of aneuploid effusion cells with a probe to 8q24 (MYC) and a centromeric probe to chromosome 8, which demonstrated amplification of the MYC oncogene in two of ten cases (20%). Finally, a potential application of basic findings in the clinical setting was tested by searching for micrometastatic cells in effusions from pancreatic cancer patients primarily negative by FISH. Two-colour FISH in combination with extensive screening (>10 000 nuclei) seems to be a useful tool to unequivocally identify micrometastatic cells by demonstrating hyperdiploidy and intranuclear chromosomal heterogeneity.