Type

Journal Article

Authors

Leonie Young
Arnold D Hill
Peadar O'Gaora
Paul S Tibbitts
Lance Hudson
Marie McIlroy
Jarlath C Bolger
Christopher Byrne
Sinéad Cocchiglia
Damir Vareslija
and 4 others

Subjects

Medicine & Nursing

Topics
extracellular matrix transcriptomic profile breast cancer patients disease progression global breast cancer cancer therapy focal adhesions

Transcriptomic profiling of sequential tumours from breast cancer patients provides a global view of metastatic expression changes following endocrine therapy. (2014)

Abstract Disease recurrence is a common problem in breast cancer and yet the mechanisms enabling tumour cells to evade therapy and colonise distant organs remain unclear. We sought to characterise global expression changes occurring with metastatic disease progression in the endocrine resistant setting. Here, for the first time, RNAsequencing has been performed on matched primary, nodal and liver metastatic tumours from tamoxifen-treated patients following disease progression. Expression of genes commonly elevated in the metastases of sequenced patients was subsequently examined in an extended matched patient cohort with metastatic disease from multiple sites. The impact of tamoxifen treatment on endocrine resistant tumours in vivo was investigated in a xenograft model. The extent of patient heterogeneity at the gene level was striking. Less than 3% of the genes differentially expressed between sequential tumours were common to all patients. Larger divergence was observed between primary and liver tumours than between primary and nodal tumours, reflecting both the latency to disease progression and the genetic impact of intervening therapy. Furthermore, an endocrine-resistant in vivo mouse model demonstrated that tamoxifen treatment has the potential to drive disease progression and establish distant metastatic disease. Common functional pathways altered during metastatic, endocrine-resistant progression included extracellular matrix receptor interactions and focal adhesions. This novel global analysis highlights the influence of primary tumour biology in determining the transcriptomic profile of metastatic tumours, as well as the need for adaptations in cell-cell communications to facilitate successful tumour cell colonisation of distant host organs.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Leonie Young, Arnold D Hill, Peadar O'Gaora, Paul S Tibbitts, Lance Hudson, Marie McIlroy, Jarlath C Bolger, Christopher Byrne, Sinéad Cocchiglia, Damir Vareslija and 4 others

Experts in our system

1
Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
 
2
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110
 
3
Peadar O'Gaora
University College Dublin
Total Publications: 11
 
4
Paul Tibbitts
Royal College of Surgeons in Ireland
Total Publications: 11
 
5
Lance Hudson
Royal College of Surgeons in Ireland
Total Publications: 11
 
6
Marie McIlroy
Royal College of Surgeons in Ireland
 
7
Christopher Byrne
Royal College of Surgeons in Ireland
Total Publications: 13
 
8
Sinéad Cocchiglia
Royal College of Surgeons in Ireland
Total Publications: 10
 
9
Damir Vareslija
Royal College of Surgeons in Ireland
Total Publications: 6