Bärlund Maarit, Monni Outi, Weaver J Donald, Kauraniemi Päivikki, Sauter Guido, Heiskanen Mervi, Kallioniemi Olli-P, Kallioniemi Anne
Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Genes Chromosomes Cancer. 2002 Dec;35(4):311-7. doi: 10.1002/gcc.10121.
In breast cancer, several chromosomal sites frequently undergo amplification, implicating the location of genes important for tumor development and progression. Here we cloned two novel genes, breast carcinoma amplified sequence 3 (BCAS3) and 4 (BCAS4), from the two most common amplification sites in breast cancer, 17q23 and 20q13. The BCAS3 gene at 17q23 spans more than 600 kb at the genomic level and was predicted to encode a 913 amino acid nuclear protein. The BCAS4 gene at 20q13.2 encodes a 211 amino acid cytoplasmic protein. Both BCAS3 and BCAS4 represent novel genes with no homologies to any other known gene or protein. In the MCF7 breast cancer cell line, the BCAS3 and BCAS4 genes were co-amplified, and cloning of a highly overexpressed 1.3-kb transcript revealed a rearrangement fusing the last two exons of BCAS3 with BCAS4. The fusion led to a novel message in which only the first exon of BCAS4 and part of exon 23 of BCAS3 were transcribed. The BCAS4-BCAS3 fusion transcript was detected only in MCF7 cells, but the BCAS4 gene was also overexpressed in nine of 13 breast cancer cell lines. In conclusion, our results indicate that these novel genes, BCAS3 at 17q23 and BCAS4 at 20q13.2, undergo amplification, overexpression, and fusion in breast cancer and therefore may have a role in the frequent chromosomal alterations affecting these two loci.
在乳腺癌中，几个染色体位点经常发生扩增，这表明了对肿瘤发生和进展至关重要的基因所在位置。在此，我们从乳腺癌中两个最常见的扩增位点17q23和20q13克隆了两个新基因，即乳腺癌扩增序列3（BCAS3）和4（BCAS4）。位于17q23的BCAS3基因在基因组水平上跨度超过600 kb，预计编码一个含913个氨基酸的核蛋白。位于20q13.2的BCAS4基因编码一个含211个氨基酸的胞质蛋白。BCAS3和BCAS4均代表与任何其他已知基因或蛋白质无同源性的新基因。在MCF7乳腺癌细胞系中，BCAS3和BCAS4基因共同扩增，对一个高度过表达的1.3 kb转录本进行克隆，结果显示BCAS3的最后两个外显子与BCAS4发生重排融合。这种融合产生了一个新的转录本，其中仅转录了BCAS4的第一个外显子和BCAS3的第23外显子的一部分。BCAS4 - BCAS3融合转录本仅在MCF7细胞中检测到，但BCAS4基因在13个乳腺癌细胞系中的9个中也过表达。总之，我们的结果表明，位于17q23的BCAS3和位于20q13.2的BCAS4这两个新基因在乳腺癌中发生扩增、过表达和融合，因此可能在影响这两个位点的频繁染色体改变中发挥作用。
