Multiple Cooperating Oncogenes Drive Recurrent Breast Cancer-Associated Chromosomal Amplifications: Creation of Isogenic Human Cell Line Models.

摘要

Targeted therapy for cancer is based upon the notion that tumors have characteristics that are quantitatively or qualitatively different from normal tissues, or that tumor cells are uniquely dependent, or addicted , to certain of these characteristic differences. Genetic changes including somatic mutation, gene amplification, and chromosomal translocation often serve as irreversible drivers of tumor growth and survival making them attractive targets for therapy. The amplification of ERBB2/Her-2 on chromosome 17q12 in 15% of breast cancers led to the identification of Her-2 as a driver oncogene and successful target for therapy. Other chromosomal regions are recurrently amplified in breast cancer almost as frequently as 17q12: these include 8p11-12 and 11q13. Amplification of 8p11-12 has been shown to confer a high risk of metastasis after primary breast cancer surgery and adjuvant therapy, and it is therefore critical to identify the oncogene(s) driving this aggressive behavior.