Multiple genetic alterations involved in the tumorigenesis of human cholangiocarcinoma: a molecular genetic and clinicopathological study

被引:39
作者
Cong, WM [1 ]
Bakker, A
Swalsky, PA
Raja, S
Woods, J
Thomas, S
Demetris, AJ
Finkelstein, SD
机构
[1] Oriental Hepatobiliary Surg Hosp, Dept Pathol, Shanghai 200438, Peoples R China
[2] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA
关键词
cholangiocarcinoma; tumor suppressor gene; loss of heterozygosity; pathology; clinical prognosis;
D O I
10.1007/s004320000194
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Cholangiocaroinoma (CC) is the second most common malignant tumor in the liver and the molecular genetic alterations involved in the tumorigenesis of CC have not been well studied. Patients and methods: The authors analyzed the loss of heterozygosity (LOH) in four tumor suppressor genes- including the adenomatous polyposis coli (APC) gene, the deleted in colon cancer (DCC) gene. the 8-hydroguanine-specific DNA glycosylase (OGG1) gene, and the p53 gene in 22 surgically resected primary CCs by using microdissection-based PCR amplification and direct DNA sequencing. Results: A total of 19 (86.49%) out of 22 CCs exhibited genetic alterations, of which 11 (57.9%) and eight (42.1%) cases showed one and more than one gene alterations, respectively. The frequency of genetic alterations of the four genes studied ranged in order from high to low as APC (68.8%) > DCC (46.2%) > OGC1 (41.7%) > p53 (37.5%). Based on the pattern of altered genes and their correlation with clinical and pathological parameters, the genetic alterations were classified into three groups: group I: no detectable genetic alterations (n = 3. 13.6%): group II: LOH in APC and/or DCC (n = 9, 40.9%); and group III: LOH in OGG1 and/or p53 occurred separately or combined with LOH in APC and/or DCC (n = 10, 45.5%). The 23-year survival rates between group II and group III are 88.9% and 30%, respectively (P < 0.05). No significant differences were found between genetic alterations and tumor size, tumor type, tumor invasion, TNM staging, and tumor differentiation (P > 0.05). Conclusion: Accumulation of multiple genetic alterations are involved in the tumorigenesis of CC, of which, genetic alterations of APC and DCC occur at a relatively early stage, and of OGG1 and p53 occur at a relatively late stage during development of CC.
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页码:187 / 192
页数:6
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