GENE AMPLIFICATION IN HUMAN BREAST TUMORIGENESIS

描述(改编自《研究者摘要》)：基因扩增 是人类中最普遍的遗传异常形式之一 乳腺癌。然而，在癌细胞中检测到这种异常， 主要局限于克隆的那些染色体片段 已经有了扩增基因的探针。最近的应用 染色体显微切割与比较基因组杂交 技术已经导致了新的扩增染色体的鉴定 乳腺癌细胞中的片段(扩增片段)，即使在没有任何先前的 关于在这些片段上扩增的基因的知识。另外， 显微切割技术从扩增产物中分离DNA 细胞遗传学结构(均匀染色的区域和双微米 染色体)也为我们提供了匿名的扩增染色体区域 有助于在肿瘤中看到的扩增物的物理图谱的特定探针 细胞。这些研究揭示了染色体20q13是一种新的扩增子 约18%的原发乳腺肿瘤与 侵袭性肿瘤表型。这项提议的广泛长期目标是 就是分离通常被扩增和过度表达的基因 新扩增子及其在人类发育中的意义 乳腺癌。具体目标是：1)确定最小公约数 新发现的20q13扩增子的扩增区域 原发肿瘤；2)分离共同编码过表达基因 20q13扩增子的区域；3)评价它们的意义 在肿瘤组织表型背景下过度表达的基因。

DESCRIPTION (Adapted from the Investigator's Abstract): Gene amplification is one of the most pervasive forms of genetic abnormality occurring in human breast cancers. Detection of this abnormality in cancer cells has, however, mostly been limited to those segments of the chromosomes from which cloned probes for the amplified genes were already available. Recent application of chromosome microdissection and comparative genomic hybridization (CGH) techniques have led to the identification of novel amplified chromosomal segments (amplicons) in breast cancer cells even in the absence of any prior knowledge about the genes amplified on these segments. Additionally, microdissection mediated isolation of DNA from amplification implicating cytogenetic structures (homogeneously stained regions and double minute chromosomes) have also provide us with anonymous amplified chromosome region specific probes helpful in physical mapping of the amplicons seen in tumor cells. These studies have revealed chromosome 20q13 as a novel amplicon in about 18% of primary breast tumors showing strong association with aggressive tumor phenotypes. The broad long term objective of this proposal is to isolate commonly amplified and over-expressed genes encoded on the novel amplicon and evaluate their significance in the development of human breast cancer. The specific aims are: 1) to determine the minimum common region of amplification spanning the newly identified 20q13 amplicon in primary tumors; 2) to isolate the over-expressed genes encoded in the common region of 20q13 amplicon; and 3) to evaluate the significance of these over-expressed genes in the context of tumor tissue phenotypes.