Soini Y, Welsh J A, Ishak K G, Bennett W P
Department of Pathology, University of Oulu, Finland.
Carcinogenesis. 1995 Nov;16(11):2879-81. doi: 10.1093/carcin/16.11.2879.
Angiosarcomas of the liver are rare, malignant cancers composed of neoplastic blood vessels. Human hapatic angiosarcomas have been associated with liver cirrhosis or exposure to vinyl chloride, Thorotrast or arsenic. A recent analysis of six hepatic angiosarcomas associated with vinal chloride exposure found three mutations and all were A:T --> T:A transversions, which are otherwise uncommon in human cancers. To test the specificity of this mutation spectrum, we analyzed 21 hepatic angiosarcomas not associated with vinyl chloride exposure. Four cases were exposed to Thorotrast, none had a history of arsenic exposure and the rest were sporadic. Exons 5-8 of the p53 gene were amplified by polymerase chain reaction, and the products were sequenced directly. Two G:C --> A:T transitions were found in two tumors: TGCstop in codon 136. Neither mutation was associated with Thorotrast exposure. These data indicate that p53 mutations are uncommon in sporadic hepatic angiosarcomas (2/21, 9%), and the mutational profile is consistent with endogenous mechanisms. Both features support the evidence linking vinyl chloride exposure to hepatic angiosarcomas containing an increased frequency of p53 mutations with a mutational spectrum (i.e. A:T --> T:A transversions) characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride.
肝血管肉瘤是一种罕见的由肿瘤性血管构成的恶性肿瘤。人类肝血管肉瘤与肝硬化或接触氯乙烯、钍造影剂或砷有关。最近一项对6例与氯乙烯接触相关的肝血管肉瘤的分析发现了3个突变，且均为A:T→T:A颠换，而这种情况在人类癌症中并不常见。为了检验这种突变谱的特异性，我们分析了21例与氯乙烯接触无关的肝血管肉瘤。其中4例接触过钍造影剂，无一例有砷接触史，其余为散发性病例。通过聚合酶链反应扩增p53基因的第5至8外显子，并直接对产物进行测序。在两个肿瘤中发现了两个G:C→A:T转换：密码子136处为TGC终止密码子。这两个突变均与钍造影剂接触无关。这些数据表明，p53突变在散发性肝血管肉瘤中并不常见（2/21，9%），且突变谱与内源性机制一致。这两个特征都支持了将氯乙烯接触与p53突变频率增加且具有氯乙烯致癌代谢物环氧乙烷特征性突变谱（即A:T→T:A颠换）的肝血管肉瘤相联系的证据。
