Cong W M, Bakker A, Swalsky P A, Raja S, Woods J, Thomas S, Demetris A J, Finkelstein S D
Department of Pathology, Oriental Hepatobiliary Surgery Hospital, Shanghai, 200438, PR China.
J Cancer Res Clin Oncol. 2001;127(3):187-92. doi: 10.1007/s004320000194.
Cholangiocarcinoma (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.
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.
A total of 19 (86.4%) 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%) > OGG1 (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 > or = 3-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).
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.
胆管癌（CC）是肝脏中第二常见的恶性肿瘤，而参与CC肿瘤发生的分子遗传学改变尚未得到充分研究。
作者通过基于显微切割的聚合酶链反应（PCR）扩增和直接DNA测序，分析了22例手术切除的原发性CC中四个肿瘤抑制基因的杂合性缺失（LOH）情况，这四个基因包括腺瘤性息肉病 coli（APC）基因、结肠癌缺失（DCC）基因、8-羟基鸟嘌呤特异性DNA糖基化酶（OGG1）基因和p53基因。
22例CC中共有19例（86.4%）表现出基因改变，其中11例（57.9%）和8例（42.1%）分别显示一个和一个以上的基因改变。所研究的四个基因的基因改变频率从高到低依次为APC（68.8%）>DCC（46.2%）>OGG1（41.7%）>p53（37.5%）。根据改变基因的模式及其与临床和病理参数的相关性，基因改变分为三组：第一组：未检测到基因改变（n = 3，13.6%）；第二组：APC和/或DCC中的LOH（n = 9，40.9%）；第三组：OGG1和/或p53中的LOH单独出现或与APC和/或DCC中的LOH合并出现（n = 10，45.5%）。第二组和第三组的3年及以上生存率分别为88.9%和30%（P < 0.05）。基因改变与肿瘤大小、肿瘤类型、肿瘤侵袭、TNM分期和肿瘤分化之间未发现显著差异（P > 0.05）。
多种基因改变的积累参与了CC的肿瘤发生，其中APC和DCC的基因改变发生在相对早期，而OGG1和p53的基因改变发生在CC发展的相对晚期。
