Accession Number : ADA584664


Title :   Histone Code Modulation by Oncogenic PWWP-domain Protein in Breast Cancers


Descriptive Note : Annual rept. 1 Jun 2012-31 May 2013


Corporate Author : WAYNE STATE UNIV DETROIT MI


Personal Author(s) : Yang, Zeng-Quan


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA584664


Report Date : Jun 2013


Pagination or Media Count : 18


Abstract : Amplification of 8p11-12 occurs in approximately 15% of human breast cancer (HBC), and this region of amplification is significantly associated with disease-specific survival and distant recurrence in breast cancer patients (1-5). Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon to identify candidate oncogenes in breast cancer (4). We identified Wolf-Hirschhorn syndrome candidate 1- like 1 (WHSC1L1) as a candidate oncogene based on statistical analysis of copy number increase and overexpression (4). The WHSC1L1 gene encodes a PWWP domain protein that regulates gene transcription and differentiated function of cells through regulation of histone methylation (6, 7). In this proposal, we hypothesize that WHSC1L1 is the major driving oncogene in the 8p11 amplicon that is found in aggressive forms of ER positive, luminal breast cancers. Furthermore, we hypothesize that genetic deregulation of WHSC1L1 induces alterations in the epigenetic histone code resulting in the acquisition of cancer stem cell phenotypes. Based on this hypothesis, we predict that WHSC1L1 will be a good therapeutic target in breast cancer, particularly for those ER positive breast cancers that are, or become, refractory to endocrine therapy.


Descriptors :   *BREAST CANCER , *GENES , *HISTONES , CELLS(BIOLOGY)


Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE