Translational Cancer Genomics (TCG)

Next generation sequencing of breast and colorectal cancer genomes/transcriptomes

In this workgroup, it is our ambition using various genomics tools (RNA sequencing; next generation sequencing) to discover and validate new prognostic and predictive markers for breast and colorectal cancer providing insight into molecular mechanisms of disease progression and therapy failure. Using this knowledge it is our ambition to offer patients the best possible choice of treatment.

Circulating biomarkers in various solid tumors

To understand the evolution of metastatic cancer towards therapy resistance we study the temporal variation in various types of circulating biomarkers (circulating tumor cells (CTCs) and circulating endothelial cells (CECs); circulating nucleic acids (ctDNA/ctRNA) and exosomes) during therapy. Focus: breast, colorectal and prostate cancer.

Genomics studies in breast and colorectal cancer:

• Role of APOBEC mutagenesis in breast cancer progression
• Whole genome sequencing of metastatic breast and colorectal cancer to chart the landscape of metastatic disease
• Single circulation tumor cell genomics to understand clinical relevance of tumor heterogeneity
• RNA sequencing of breast cancer and rare subtypes such as male and inflammatory breast cancer

Liquid biopsy Studies:

• CareMore: Determines the clinical significance of ER en HER2 status of CTC for success rate of endocrine and trastuzumab therapy
• CTC-cDDP: Gene expression profiling of CTCs to predict cisplatin failure in metastatic breast cancer 
• TAX-ESR1: Study the ESR1 mutation status conversion rate during taxane based chemotherapy
• SONIA ctDNA: Significance of ctDNA in patient treated with AI alone on AI with a cdk4/6 inhibitor in the first and second line
• CABAv7: Significance of ARv7 status of CTCs and treatment failure in mCRPC
• MIRACLE: Predictive value of various liquid biopsy on progression after isolated liver metastasis in mCRC

Smid M, Wilting SM, Uhr K, … Foekens JA, Sieuwerts AM, Martens JWM. The circular RNome of primary breast cancer.
Genome Res. 2019 Mar;29(3):356-366.

Onstenk W, Sieuwerts AM, Kraan J, Van M, Nieuweboer AJ, Mathijssen RH, Hamberg P, Meulenbeld HJ, De Laere B, Dirix LY, van Soest RJ, Lolkema MP, Martens JW, van Weerden WM, Jenster GW, Foekens JA, de Wit R, Sleijfer SEfficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells. Eur Urol. 2015 Dec;68(6):939-45.

Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW.
Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer.
Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13021-6

Sieuwerts AM, Mostert B, Bolt-de Vries J, Peeters D, de Jongh FE, Stouthard JM, Dirix LY, van Dam PA, Van Galen A, de Weerd V, Kraan J, van der Spoel P, Ramírez-Moreno R, van Deurzen CH, Smid M, Yu JX, Jiang J, Wang Y, Gratama JW, Sleijfer S, Foekens JA, Martens JW. mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients.
Clin Cancer Res. 2011 Jun 1;17(11):3600-3618

Collaboration within Erasmus MC:

• Dept of Pathology (prof. W. Dinjens, dr. C. van Deurzen, prof. R. Fodde)
• Dept of Surgery (prof. C. Verhoef, prof. J. IJzermans)
• Urology Dept of (prof. G Jenster; dr. W van Weerden)
• Dept of Molecular Genetics (dr. D van Gent)
• Dept of Developmental Biology (prof. J Gribnau)

Collaboration outside of Erasmus MC:

• Paul. Span, Radboud University Medical Centre, Nijmegen
• Bob van de Water, Leiden University, Leiden
• Leon Terstappen, University of Twente, Enschede
• Reuben Harris, University of Minnesota, Minnesota, USA
• Steven van Laere University of Antwerp, Antwerp, Belgium
• Serena Nik-Zainal. Cancer research UK, Cambridge, UK
• Fred Sweep, Radboud University Medical Centre, Nijmegen
• Jaap den Toonder, Eindhoven University of Technology
• Erik Danen, Leiden University, Leiden
• Peter ten Dijke, Leiden University Medical Center
• Jos Jonkers, Netherlands Cancer Institute, Amsterdam
• Lodewijk Wessels, Netherlands Cancer Institute, Amsterdam
• Ester Lips, Netherlands Cancer Institute, Amsterdam
• Wilbert Zwart, Netherlands Cancer Institute, Amsterdam
• Carolien Shröder. UMC Groningen, Groningen

1. NWO zwaartekracht 2012: Cancer genomics consortium Netherlands (CGC.nl)

2. NKB NKI2014-7080: Genetic causes of resistance to new androgen receptor signaling inhibitors in circulating tumor DNA of metastasized castration resistant prostate cancer patients

3. NKB EMCR 2014−7087: Cranking up tumor-specific T cell responses in metastatic breast cancer

4. NKB RUG 2013−6267: INFLAME: towards optimal treatment of inflammatory breast cancer patients PIs

5. NKB EMCR 10270 2016: The role of APOBEC3B in breast cancer therapy resistance

6. NKB EMC 10823 2016: Is ESR1 mutational status measured in cell-free DNA associated with outcome to first-line taxane-based chemotherapy in ER-positive HER2-negative MBC patients? 

7. Daniel den Hoed Stg 2017: Development single circulating tumour cell diagnostics

8. NKB EMCR 11708 2018: Prediction of early recurrence in patients with resectable colorectal cancer liver metastasesusing a blood-based expression profile

9. NKB EMCR 12039 2019: Detection of early progression by circulating tumor DNA in metastatic breast cancer patients treated with endocrine therapy and CDK4/6-inhibitors 

10. BC Now 8308 2019:The value of circulating tumor DNA dynamics in patient selection for palbociclib treatment 

11. MLDS 2018: Prediction of early recurrence in patients with resectable colorectal cancer liver metastasesusing a blood-based expression profile

John Martens, professor, Principal investigator

Team Members:

• Dr. Saskia Wilting
• Dr. Stavros Makrodimitris
• Dr. Jaco Kraan
• Dr. Erik Kreiter
• Dr. Sridhar Kandala
• Dr. Khrystany Isebia
• Dr. Maurice Jansen
• Rosita Pherai- Nanhkoesingh
• Marcel Smid
• Vanja de Weerd
• Corine Beaufort
• Kirsten Ruigrok
• Patricia van Kuijk
• Mieke Timmermans
• Jean Helmijr
• Mai Van
• Tanja van Dijk
• Bram Pronk
• Daan Hazelaar
• Hamdy Warda
• Lotte van Leeuwen
• Maria Bordoy Coma-Cros
• Noor Wortelboer
• Shuoying Qu
• Youssra Salhi
• Zhangzan Huang
  

For questions please mail to r.pherai@erasmusmc.nl.