Bartsch D, Barth P, Bastian D, Ramaswamy A, Gerdes B, Chaloupka B, Deiss Y, Simon B, Schudy A
Department of Surgery, Philipps-University Marburg, Germany.
Cancer Lett. 1999 May 3;139(1):43-9. doi: 10.1016/s0304-3835(98)00380-2.
The tumor suppressor gene DPC4/Smad4 at 18q21.1 is inactive in about 50% of pancreatic carcinoma xenografts and cell lines. However, the role of DPC4 in the multistep carcinogenesis of primary pancreatic adenocarcinomas remains uncertain. Therefore, we examined 45 primary human pancreatic adenocarcinomas and 12 pancreatic cancer cell lines for DPC4 alterations by single-strand conformational variant (SSCV) analysis and a PCR-based deletion assay. DPC4 was inactivated by either homozygous deletion or point mutation in 6 of 12 cell lines (50%). None of the primary pancreatic carcinomas carried a DPC4 mutation, although 66% revealed LOH of 18q21 sequences. These findings suggest that inactivation of DPC4 occurs more frequently in tumor-derived cell lines than in primary pancreatic adenocarcinomas. In addition, another, yet unidentified, tumor suppressor gene(s) may be linked with the frequent LOH of 18q21 in primary pancreatic adenocarcinomas.
位于18q21.1的肿瘤抑制基因DPC4/Smad4在约50%的胰腺癌异种移植瘤和细胞系中失活。然而，DPC4在原发性胰腺腺癌多步骤致癌过程中的作用仍不确定。因此，我们通过单链构象变异（SSCV）分析和基于PCR的缺失检测，检测了45例原发性人胰腺腺癌和12个胰腺癌细胞系中的DPC4改变。12个细胞系中有6个（50%）通过纯合缺失或点突变使DPC4失活。原发性胰腺癌均未携带DPC4突变，尽管66%显示18q21序列杂合性缺失（LOH）。这些发现表明，DPC4失活在肿瘤衍生细胞系中比在原发性胰腺腺癌中更频繁发生。此外，另一个尚未确定的肿瘤抑制基因可能与原发性胰腺腺癌中频繁出现的18q21 LOH有关。
