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Master Thesis

Mise au point d’un test de dépistage des tumeurs séreuses de haut grade chez des femmes à risques. Analyse simultanée des aneuploïdies (CNV) et du statut TP53 sur ADN FFPE tumoral et ADN plasmatique circulant par capture NGS Oneseq

Abstract : High grade serous carcinomas (HGSC) are poor prognostic cancers that are more likely to occur in women at risk, carrying a deleterious mutation in a predisposition gene. Periodic follow-up of these at-risk women with an adapted screening test could allow early diagnosis to improve the prognosis. The genetics of HGSC is characterized by the association of a mutation on the TP53 gene in 95% of cases, and numerous aneuploidies (amplifications, gains or losses of DNA). Our work consisted in using the Oneseq NSG process to evaluate the feasibility of a screening test detecting these abnormalities in the cell-free DNA (cfDNA) of women at risk of HGSC. The sample consisted of 15 patients with HGSC for whom we have tumor FFPE DNA and a sample of cfDNA. The Oneseq NGS process was first developed on FFPE DNA in comparison with an SNP array technique, and found 14/15 patients (93%) with a TP53 mutation and 13/15 (87%) with tumor aneuploidies. The tumor origin of the aneuploidies was confirmed by comparison with the TCGA datas (The Cancer Genome Atlas). These results show that the Oneseq NGS is relevant for HGSC FFPE DNA analysis, with simultaneous detection of aneuploidies and point mutations. In the second part, the analysis by Oneseq NGS of cfDNA samples from sick patients did not detect genetic abnormalities of tumor origin. An evaluation of the sensitivity of detection of aneuploidies and TP53 mutations in cfDNA suggests that Oneseq NGS is not suitable for the early detection of HGSC in at-risk women.
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Master Thesis
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Louis Lebreton. Mise au point d’un test de dépistage des tumeurs séreuses de haut grade chez des femmes à risques. Analyse simultanée des aneuploïdies (CNV) et du statut TP53 sur ADN FFPE tumoral et ADN plasmatique circulant par capture NGS Oneseq. Sciences du Vivant [q-bio]. 2020. ⟨dumas-02937649⟩

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