Exploring novel cancer-related genes within novel amplifications detected by CGH in gastrointestinal tumors

越来越多的证据表明，在胃肠道肿瘤的致癌过程中，在核苷酸水平和染色体水平上顺序发生的多个基因改变是胃肠道肿瘤发生过程的基础。染色体DNA的扩增是能够激活与肿瘤发生有关的基因的机制之一。已知癌基因如CCND1(11q13)和MYC(8q24)在几种类型的癌症中通过扩增而被激活。比较基因组杂交(CGH)研究是探索其他扩增区域的有力工具。因此，我们对实体肿瘤，特别是胃肠道肿瘤的拷贝数异常进行了广泛的分析，以探索新的扩增区域并确定扩增片段中的靶基因。利用mis策略，我们发现了一些新的靶基因，包括GASC1(9p23)、cIAP1(11q22)、TGIF2(18p11.3)、SNO和Evil(3q26-27)、HNF2A(14q12-13)、CEMPF和ATF3(1q32)和IQGAP1(15q26&gt；此外，我们还构建了如下高密度CGH阵列系统：(1)在整个基因组中包含4500个BAC的阵列，(2)包含800个癌症相关基因的“个性化医学”阵列，以及(3)包含212个BAC的阵列，该阵列跨越染色体1p36上的20Mb重叠群。我们的CGH阵列为探索与胃肠道肿瘤分子发病机制相关的隐性染色体拷贝数异常打开了窗口。

Accumulated evidence suggests that multiple genetic alterations occurring sequentially in a cell lineage, at the nucleotide levels as well as at the chromosome levels, underlie the carcinogenetic process in gastrointestinal tumors. Amplification of chromosomal DNA is one of the mechanisms capable of activating genes that are implicated in developing tumors. Oncogenes such as CCND1 (11q13) and MYC (8q24) are known to be activated by amplification in several types of cancer. Comparative genomic hybridization (CGH) studies is the powerful tool for exploring additional regions of amplification. Thus we perform extensive analysis of copy number aberration in solid tumors, especially in gastrointestinal tumors, to explore novel amplified regions and identify target genes within the amplicons. By using mis strategy, we have identified novel target genes including GASC1 (9p23), cIAP1 (11q22), TGIF2 (18p11.3), SNO and Evil (3q26-27), HNF2A (14q12-13), CEMPF and ATF3 (1q32), and IQGAP1 (15q26>. Furthermore, we have constructed high-density CGH array system as follows; (1) An array harboring 4500 BACs throughout a whole genome, (2) An array containing 800 cancer-related genes for "personalized medicine", and (3) An array harboring 212 BACs spanning the 20 Mb contig at chromosome 1p36. Our CGH array can open the window for exploring cryptic chromosome copy number aberrations relevant with molecular pathogenesis in gastrointestinal tumors.