CRAN - Campus Sciences
BP 70239 - 54506 VANDOEUVRE Cedex
Tél : +33 (0)3 72 74 52 90
Sujet de stage : Détection de l'ADN tumoral circulant chez les patients atteints d'une tumeur solide
Dates : 2017/06/06 - 2017/08/31
Directeur(s) CRAN : Alexandre HARLE
Description : Development of targeted therapies has been a real progress for the treatment of patients with cancer.
Progression-free survival (PFS) and Overall survival (OS) have been extended for a large sort of cancers like lungs,
ovarian or melanomas. The use of anti-EGFR kinase inhibitors (gefitinib and erlotinib) considerably improved PFS
and OS in patients with non-small cell lungs cancer (NSCLC) bearing an activating mutation of EGFR (Mok et al.,
2009, Shepherd et al. 2005). More recently, the use of osimertinib also improved PFS and OS in patients with a
resistant T790M mutation of EGFR (Mok et al., 2016). Anti-BRAF kinase inhibitors vemurafenib and dabrafenib
associated with anti-MEK kinase inhibitors cobimetinib and trametinib respectively were also a significate
improvement for the treatment of patients with metastatic melanoma bearing a V600 BRAF mutation (Flaherty et
al., 2012, Larkin et al., 2014). PFS and OS have also been improved in women with a high grade platine-sensitive
bearing a germinal or somatic mutation of BRCA1/2 ovarian cancer with the use of the anti-PARP olaparib
(Ledermann et al., 2012). Most targeted therapies are kinase inhibitors and require assessing somatic mutations
on DNA tumor to ensure the absence of resistance (Moses et al., 2016). Nevertheless, even if the mutation
responsible for resistance is not detected, a majority of patients do not benefit from the targeted treatment. It is
now described that solid tumors are heterogeneous and contain a large number of different subclones (Allison
and Sledge, 2014). The detection of these different subclones from a single tumor sample is rarely possible with
common techniques like PCR or NGS. We know that during their development, cancer cells may undergo
apoptosis or necrosis but also can excrete content with exosomes. The DNA of the cancer cells is then released in
biological fluids like blood in the form of cell-free DNA, or ctDNA (Bettegowda et al., 2014). The improvement of
molecular assays sensitivity now allows the detection of this ctDNA and it is under investigation that ctDNA may
be a mirror of cancer heterogeneity (Murtaza et al., 2015).

Recent advances in personalized medicine have led to the development of multiplex genomic analyses for clinical
use. It is now recognized that next-generation sequencing of tumors has convincing analytical validity (Swanton et
al., 2016) and a lot of evidences also show that this assay is ready for the detection of circulating free DNA and
can be used in routine diagnosis for disease monitoring (Jiang et al., 2016, Gray et al., 2015).

We propose to analyze ctDNA extracted from samples of patients with solid tumors. These samples will be
collected at different stage of the disease. NGS and high-sensitivity PCR assays will be used for the detection of
Mots clés : cancer, ctDNA, NGS, PCR, monitoring
Conditions : Stage d'initiation à la recherche (SIR)
Durée : 2 mois ou 44 jours
Employeur et lieu : Service de Biopathologie / Institut de Cancérologie de Lorraine
Rémunération : Non rémunéré
Profil : étudiant en DFA-SP1
Département(s) :
Biologie, Signaux et Systèmes en Cancérologie et Neurosciences
Financement : sans objet