Lammie G A, Fantl V, Smith R, Schuuring E, Brookes S, Michalides R, Dickson C, Arnold A, Peters G
Imperial Cancer Research Fund Laboratories, St Bartholomew's Hospital, London, UK.
Oncogene. 1991 Mar;6(3):439-44.
Approximately 15 to 20% of primary breast cancers and an even higher proportion of squamous cell carcinomas of the head and neck show amplification of DNA markers on band q13 of human chromosome 11. However, known genes within the amplified region, such as the FGF-related oncogenes INT-2 and HST-1, are very rarely expressed in these tumors. Here we show that another candidate oncogene, designated D11S287, implicated in the pathogenesis of parathyroid adenomas, is also amplified in breast cancers. Significantly, it is consistently coamplified with INT-2 and HST-1 in 36 out of 202 primary tumors, including one case in which the amplified unit did not encompass the translocation breakpoint marker BCL-1. This implies that D11S287 is on the same side of the breakpoint as INT-2, and pulsed-field gel electrophoresis indicates that D11S287 is less than 250 kb from the BCL-1 marker. Since D11S287 RNA was present at elevated levels in a group of tumors and cell lines in which the 11q13 region is amplified, it may be the key oncogene on this amplified unit, and could also be activated by BCL-1 translocations.
大约15%至20%的原发性乳腺癌以及更高比例的头颈部鳞状细胞癌显示人类染色体11 q13带上的DNA标记物发生扩增。然而,扩增区域内的已知基因,如FGF相关癌基因INT-2和HST-1,在这些肿瘤中很少表达。我们在此表明,另一个候选癌基因,命名为D11S287,与甲状旁腺腺瘤的发病机制有关,在乳腺癌中也发生了扩增。值得注意的是,在202例原发性肿瘤中的36例中,它与INT-2和HST-1始终共同扩增,其中包括1例扩增单元不包含易位断点标记物BCL-1的病例。这意味着D11S287与INT-2位于断点的同一侧,脉冲场凝胶电泳表明D11S287距离BCL-1标记物不到250 kb。由于在一组11q13区域发生扩增的肿瘤和细胞系中,D11S287 RNA水平升高,它可能是这个扩增单元上的关键癌基因,也可能被BCL-1易位激活。