Giardiello F M, Petersen G M, Brensinger J D, Luce M C, Cayouette M C, Bacon J, Booker S V, Hamilton S R
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Gut. 1996 Dec;39(6):867-9. doi: 10.1136/gut.39.6.867.
Hepatoblastoma is a rare, rapidly progressive, usually fatal childhood malignancy, which if confined to the liver can be cured by radical surgical resection. An association between hepatoblastoma and familial adenomatous polyposis (FAP), which is due to germline mutation of the APC (adenomatous polyposis coli) gene, has been confirmed, but correlation with site of APC mutation has not been studied.
To analyse the APC mutational spectrum in FAP families with hepatoblastoma as a possible basis to select kindreds for surveillance.
Eight patients with hepatoblastoma in seven FAP kindreds were compared with 97 families with identified APC gene mutation in a large Registry.
APC gene mutation was evaluated by RNase protection assay or in vitro synthesis protein assay. The chi 2 test and correlation were used for data analysis.
APC gene mutation was identified in all seven FAP kindreds in which an at risk member developed hepatoblastoma. A male predominance was noted (six of eight), similar to literature cases (18 of 25, p < 0.01. Mutations were restricted to codons 141 to 1230, but no significant difference in site of mutation between pedigrees with and without hepatoblastoma was identified.
Hepatoblastoma occurs primarily in boys in FAP kindreds and is associated with germline APC mutation in the 5' end of the gene. However, the site of APC mutation cannot be used to predict occurrence of this extracolonic cancer in FAP pedigrees.
肝母细胞瘤是一种罕见的、进展迅速、通常致命的儿童恶性肿瘤，若局限于肝脏，可通过根治性手术切除治愈。肝母细胞瘤与家族性腺瘤性息肉病（FAP）之间的关联已得到证实，FAP是由APC（腺瘤性息肉病 coli）基因的种系突变引起的，但与APC突变位点的相关性尚未研究。
分析伴有肝母细胞瘤的FAP家族中的APC突变谱，作为选择亲属进行监测的可能依据。
将7个FAP家族中的8例肝母细胞瘤患者与一个大型登记处中97个已鉴定出APC基因突变的家族进行比较。
通过核糖核酸酶保护试验或体外合成蛋白试验评估APC基因突变。采用卡方检验和相关性分析进行数据分析。
在所有7个有高危成员发生肝母细胞瘤的FAP家族中均鉴定出APC基因突变。观察到男性占优势（8例中的6例），与文献报道的病例相似（25例中的18例，p<0.01）。突变局限于密码子141至1230，但在有和没有肝母细胞瘤的家系之间，突变位点未发现显著差异。
在FAP家族中，肝母细胞瘤主要发生于男孩，且与该基因5'端的种系APC突变相关。然而，APC突变位点不能用于预测FAP家系中这种结肠外癌症的发生。
