Hahn S A, Schutte M, Hoque A T, Moskaluk C A, da Costa L T, Rozenblum E, Weinstein C L, Fischer A, Yeo C J, Hruban R H, Kern S E
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Science. 1996 Jan 19;271(5247):350-3. doi: 10.1126/science.271.5247.350.
About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4, a gene similar in sequence to a Drosophila melanogaster gene (Mad) implicated in a transforming growth factor-beta (TGF-beta)-like signaling pathway. Potentially inactivating mutations in DPC4 were identified in six of 27 pancreatic carcinomas that did not have homozygous deletions at 18q21.1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers.
约90%的人类胰腺癌在18号染色体长臂表现出等位基因缺失。为了鉴定18号染色体长臂上的候选肿瘤抑制基因，对一组胰腺癌进行了纯合缺失汇聚位点分析。84个肿瘤中有25个在18q21.1存在纯合缺失，该位点不包括DCC（一种结直肠癌候选抑制基因），但包括DPC4，其基因序列与果蝇中一个与转化生长因子-β（TGF-β）样信号通路相关的基因（Mad）相似。在18q21.1不存在纯合缺失的27个胰腺癌中有6个鉴定出DPC4存在潜在的失活突变。这些结果确定DPC4为候选肿瘤抑制基因，其失活可能在胰腺癌以及其他可能的人类癌症中起作用。
