Porter Dale, Lahti-Domenici Jaana, Keshaviah Aparna, Bae Young Kyung, Argani Pedram, Marks Jeffrey, Richardson Andrea, Cooper Amiel, Strausberg Robert, Riggins Gregory J, Schnitt Stuart, Gabrielson Edward, Gelman Rebecca, Polyak Kornelia
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Mol Cancer Res. 2003 Mar;1(5):362-75.
Gene expression patterns in ductal carcinoma in situ (DCIS), and in invasive, and metastatic breast tumors were determined using serial analysis of gene expression (SAGE). We used mRNA in situ hybridization to examine gene expression at the cellular level and immunohistochemistry on tissue microarrays to determine association between gene expression patterns and histopathologic characteristics of the tumors. We found that that the most dramatic transcriptome change occurs at the normal to DCIS transition, while there is no clear universal "in situ" or "invasive" tumor molecular signature. From the 16,430 transcripts analyzed, we identified only 5 and 11 that were preferentially up-regulated in DCIS and invasive tumors, respectively. The majority of invasive cancer specific SAGE tags correspond to novel genes. The genes we identified may define biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease.
利用基因表达序列分析(SAGE)确定导管原位癌(DCIS)、浸润性乳腺癌和转移性乳腺癌中的基因表达模式。我们使用mRNA原位杂交在细胞水平检测基因表达,并在组织微阵列上进行免疫组织化学,以确定基因表达模式与肿瘤组织病理学特征之间的关联。我们发现,最显著的转录组变化发生在从正常组织到DCIS的转变过程中,而没有明确的普遍“原位”或“浸润性”肿瘤分子特征。在分析的16430个转录本中,我们分别仅鉴定出5个和11个在DCIS和浸润性肿瘤中优先上调的转录本。大多数浸润性癌特异性SAGE标签对应于新基因。我们鉴定出的基因可能定义了具有进展为浸润性疾病高风险的DCIS的生物学和临床意义上的亚组。