GENE AMPLIFICATION IN HUMAN BREAST TUMORIGENESIS

人类乳腺肿瘤发生中的基因扩增

• 批准号: 2871808
• 负责人: Subrata Sen
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2871808
• 关键词: artificial chromosomes; breast neoplasm /cancer diagnosis; breast neoplasms; chromosome aberrations; clinical research; complementary DNA; computer assisted sequence analysis; cytogenetics; gene expression; genetic mapping; genetic markers; human genetic material tag; human subject; natural gene amplification; neoplasm /cancer genetics; neoplastic process; northern blottings; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence; polymerase chain reaction; radionuclides

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.

描述（改编自研究者摘要）：基因扩增 是人类遗传异常中最普遍的形式之一 乳腺癌 然而，在癌细胞中检测到这种异常， 大多数被限制在克隆的染色体片段上， 扩增基因的探针已经可用。 最新应用 染色体显微切割和比较基因组杂交（CGH） 技术已经导致鉴定新的扩增染色体 乳腺癌细胞中的片段（扩增子），即使在没有任何先前的 关于这些片段上扩增的基因的知识。 此外，本发明还 显微切割介导的DNA从扩增中分离， 细胞遗传学结构（均匀染色区域和双微 染色体）也为我们提供了匿名扩增的染色体区域 特异性探针有助于肿瘤中所见扩增子的物理作图 细胞 这些研究揭示了染色体20 q13作为一种新的扩增子， 约18%的原发性乳腺肿瘤与 侵袭性肿瘤表型。 这项建议的长远目标 是分离通常扩增和过度表达的基因编码的 新的扩增子，并评估其在人类发育中的意义 乳腺癌 具体目标是：1）确定最小共同 扩增区域跨越新鉴定的20 q13扩增子， 2）分离出在肿瘤细胞中编码的过表达基因， 20 q13扩增子的区域;和3）评估这些区域的显著性， 在肿瘤组织表型的背景下过表达的基因。

项目成果

Loss of Aurora A / STK 15 / BTAK Overexpression Correlates with Transition of in Situ to Invasive Ductal Carcinoma of the Breast

• 发表时间: 2003
• 作者: A. Hoque;J. Carter;W. Xia;M. Hung;A. Sahin;S. Sen;S. Lippman

Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer.

• 发表时间: 2003-03
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Donghui Li;Jijiang Zhu;P. Firozi;J. Abbruzzese;Douglas B. Evans;K. Cleary;H. Friess;S. Sen