MOLECULAR TYPING OF TRIPLE NEGATIVE BREAST CANCER

Abstract: 

Triple negative breast cancers (TNBCs) represent approximately 15% of breast cancers and are characterized by absence of expression of estrogen and progesterone receptors (ER/PR) and absence of HER2 overexpression. Most TNBCs display distinct clinicopathological characteristics, including high histological grade, and represent almost the exclusive phenotype in patients-carriers of BRCA1 gene mutations.

This project aims at characterizing TNBC molecular subtypes based on different molecular profiles, the IHC expression of CK5/6, Ki67, EGFR, phospho-Jun, p65-NFKB, ERbeta and its isoforms ERbeta1 and ERbeta2 and, the G2-chromosomal radiosensitivity of TNBC patients. Research will be performed in 500 tissue samples of sporadic and familial TNBC, established cell lines and peripheral blood lymphocytes of TNBC patients. Cancer genetics analysis will be performed in all 500 patients using complete family pedigrees and constitutive DNA from peripheral lymphocytes.

Clinicopathological and genetic analysis will entail,

  • investigation of BRCA1, RAD51C, PALB2 & CHEK2 genes inactivation,
  • Receptor Tyrosine Kinase pathway activation using IHC and real time PCR and
  • identification of mutant BRCA1, RAD51C, PALB2, CHEK2, STK11, CDH1 genes.

Meta-analysis of gene expression profiles will be carried out to identify gene modules describing "œdruggable" oncogenic pathways. Assessment of endogenous radiosensitivity by measurement of DNA damages response will serve as an additional marker for characterization of TNBC subtypes. Assessment of ERbeta1, ERbeta2 and ERbeta expression will address their prognostic significance in TNBC and highlight ERbeta1 potential as therapeutic target.

Determination of chromatin binding sites and transcriptional read-out of ERbeta1 in mutant or wild-type BRCA1-bearing TNBC cell lines treated with tamoxifen and/or gefitinib in the absence or presence of trichostatin A will probe the molecular determinants of the putative anticancer action of ERbeta1.

Project info

Acronym:
TNBC
Coordinating Institution:
Aristotle University of Thessaloniki
Scientific Coordinator:
Fountzilas Giorgos
Research Team 2 Leader:
Yannoukakos Drakoulis
Research Team 3 Leader:
Alexis Michael N.

Stats

I.D.:
266
Mis:
380136
Duration (months):
36
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β4Λ59-ΔΛΠ

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