47P - Loss-of-function PTPRT and PTPRD mutations predict bevacizumab resistance in metastatic colorectal cancer patients

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Translational Research
Presenter Kien Thiam Tan
Citation Annals of Oncology (2016) 27 (suppl_9): ix9-ix18. 10.1093/annonc/mdw574
Authors K.T. Tan1, S. Chen1, H. Chen1, H. Hung-Chih2
  • 1Clinical Sequencing, ACT Genomics Co. Ltd., 114 - Taipei/TW
  • 2Division Of Hematology-oncology, Chang Gung Memorial Hospital-Linkou, 333 - Taoyuan/TW

Abstract

Background

Bevacizumab is a VEGF-directed anti-angiogenic therapy for KRAS-mutated metastatic colorectal cancer (mCRC) patients. However, some patients do not benefit from the treatment and there is no appropriate biomarker for the response prediction The aim of this study was to identify genetic markers that might predict the response to bevacizumab treatment.

Methods

34 archived primary tumor tissues of stage IV mCRC cancer were analyzed, including 17 bevacizumab responders and 17 non-responders. We assessed all coding exons in 409 cancer-related genes for base substitutions, indels, and copy number alterations. The average sequencing depth was > 1,000×.

Results

We observed 414 genomic alterations in 194 genes in all tumors (mean 12.1, range 6-19). The average number of genomic alterations was similar in responder (12.1 range 3-18) and non-responders (12.2, range 7-19) tumors. The most commonly mutated in both groups genes were TP53, APC, SYNE1 and PTPRT. Pathway analyses of altered genes revealed aberration in p53, Wnt, and JAK/STAT in both groups. Up to 35% of mCRC patients harbor mutations or copy number alterations in the PTPRT or PTPRD, protein tyrosine phosphatases in the JAK/STAT pathway. Interestingly, loss-of-function mutation or copy number loss of PTPRT/PTPRD were found to be enriched in the bevacizumab resistance tumors (p = 0.0072).

Conclusions

Our data suggest that PTPRT and PTPRD loss-of-function alterations may serve as a predictive biomarker of sensitivity to bevacizumab treatment in mCRCs.

Clinical trial indentification

Legal entity responsible for the study

The study was funded by a biotech company

Funding

ACT Genomics

Disclosure

All authors have declared no conflicts of interest.