Achille A, Scupoli M T, Magalini A R, Zamboni G, Romanelli M G, Orlandini S, Biasi M O, Lemoine N R, Accolla R S, Scarpa A
Department of Anatomia Patologica, Università di Verona, Italy.
Int J Cancer. 1996 Nov 4;68(3):305-12. doi: 10.1002/(SICI)1097-0215(19961104)68:3<305::AID-IJC7>3.0.CO;2-5.
We explored APC gene mutations and chromosome 5q21 allelic losses (5qLOH) in 18 neoplasms of the papilla of Vater, including 6 early-stage tumours (3 adenomas, 3 carcinomas) and 12 advanced-stage cancers. Eleven PCR-amplified polymorphic sequences were used to analyse 5qLOH. APC mutations were investigated both by an in vitro APC-protein truncation test and by single-strand conformation polymorphism analysis. Mutations in the Ki-ras, N-ras and p53 genes were also assessed. We found: 5qLOH in 8 of 16 cases (50%), including 1 adenoma, 3 early- and 4 advanced-stage cancers; APC mutations in 2 adenomas and 1 advanced-stage carcinoma; Ki- or N-ras mutations in 3 adenomas and 3 advanced-stage cancers; p53 mutations in 2 early-stage and 7 advanced-stage adenocarcinomas. Our results suggest that 5qLOH, APC mutations and ras mutations are present at early stages, whereas p53 inactivation is associated with progression of malignancy in a large proportion of cases. These data indicate that sporadic ampullary tumours differ from those occurring in familial adenomatous polyposis in the frequency (17% vs. 64%) as well as in the site of APC somatic mutations, suggesting a different molecular pathogenesis in the 2 conditions.
我们研究了18例 Vater 乳头肿瘤中的 APC 基因突变和 5 号染色体长臂 21 区等位基因缺失（5qLOH），其中包括 6 例早期肿瘤（3 例腺瘤、3 例癌）和 12 例晚期癌。使用 11 个 PCR 扩增的多态性序列分析 5qLOH。通过体外 APC 蛋白截短试验和单链构象多态性分析研究 APC 突变。还评估了 Ki-ras、N-ras 和 p53 基因的突变。我们发现：16 例中有 8 例（50%）存在 5qLOH，包括 1 例腺瘤、3 例早期癌和 4 例晚期癌；2 例腺瘤和 1 例晚期癌存在 APC 突变；3 例腺瘤和 3 例晚期癌存在 Ki-或 N-ras 突变；2 例早期腺癌和 7 例晚期腺癌存在 p53 突变。我们的结果表明，5qLOH、APC 突变和 ras 突变在早期阶段就已存在，而在大部分病例中，p53 失活与恶性进展相关。这些数据表明，散发性壶腹肿瘤与家族性腺瘤性息肉病中的肿瘤在频率（17% 对 64%）以及 APC 体细胞突变位点方面存在差异，提示这两种情况的分子发病机制不同。
