Schenk M, Leib-Mösch C, Schenck I U, Jaenicke M, Indraccolo S, Saeger H D, Dallenbach-Hellweg G, Hehlmann R
III. Medizinische Klinik, Klinikum Mannheim, Universität Heidelberg, Germany.
J Mol Med (Berl). 1996 Mar;74(3):155-9. doi: 10.1007/BF01575448.
Inactivation of tumor suppressor genes is thought to be a critical step in tumorigenesis. The DCC (deleted in colorectal carcinoma) gene, located on the long arm of chromosome 18, has been shown to be frequently deleted in colorectal tumors. To investigate the involvement of allelic deletions on chromosome 18q in breast cancer tumorigenesis we analyzed 28 primary breast tumors and 28 colorectal tumors (24 carcinomas, 4 adenomas) with four different polymorphic DNA markers detecting RFLPs on chromosome 18q. In breast cancer we found loss of heterozygosity (LOH) in 4 of 27 (15%) informative cases whereas 15 of 25 (60%) colorectal tumors showed allelic deletions. In all cases of allelic loss the DCC locus or its proximal vicinity (locus SSAV1) were involved. LOH on chromosome 18q occurs both in breast and colorectal cancer, yet the frequency of these deletions in breast tumors is lower than in colorectal tumors. Moreover, in breast cancer these mutations were only detected in large and undifferentiated tumors.
肿瘤抑制基因的失活被认为是肿瘤发生过程中的关键步骤。位于18号染色体长臂上的DCC（结直肠癌缺失）基因，已证实在结直肠肿瘤中经常发生缺失。为了研究18q染色体上等位基因缺失在乳腺癌发生中的作用，我们使用检测18q染色体上限制性片段长度多态性（RFLP）的四种不同多态性DNA标记，分析了28例原发性乳腺癌肿瘤和28例结直肠肿瘤（24例癌，4例腺瘤）。在乳腺癌中，我们在27例（15%）信息充分的病例中有4例发现杂合性缺失（LOH），而25例（60%）结直肠肿瘤显示有等位基因缺失。在所有等位基因缺失的病例中，DCC基因座或其近端区域（基因座SSAV1）均受累。18q染色体上的杂合性缺失在乳腺癌和结直肠癌中均有发生，但这些缺失在乳腺肿瘤中的频率低于结直肠肿瘤。此外，在乳腺癌中，这些突变仅在大的未分化肿瘤中检测到。
