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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2446 - Quantifying circulating cell-free DNA as clinical biomarker

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

MEDDEB Romain

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

M. Romain1, Z.A.A. Dache1, A. Otandault1, R. Tanos1, B. Pastor1, C. Sanchez1, J. Azzi1, G. Tousch1, S. Azan1, C. Mollevi1, S. Thezenas2, P. Blache1, A.R. Thierry1

Author affiliations

  • 1 Integrated Research For The Personalized Medicine In Digestive Oncology, ICM Regional Cancer Institute of Montpellier, 34090 - Montpellier/FR
  • 2 Biostatistics, ICM Regional Cancer Institute of Montpellier, 34090 - Montpellier/FR
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Abstract 2446

Background

This is the first comprehensive study on the effect of pre-analytical and demographic parameters that could be a source of variability in the quantification of nuclear and mitochondrial circulating DNA (NcirDNA and McirDNA, respectively).

Methods

We set an optimal calculation of the simultaneous quantification of circulating nuclear and mitochondrial genome copy number based on a clinically validated q-PCR method. We report data from a total of 217 subjects, 99 healthy individuals and 118 metastatic colorectal cancer (mCRC) patients. We also investigated the influence of blood storage and collection time on cirDNA concentration from healthy volunteers.

Results

Approximately 26,650 and 3,000-fold more mitochondrial than nuclear genome copies were found in healthy subjects and mCRC patients, respectively. Neither NcirDNA nor McirDNA plasma concentrations depended on age in the healthy and mCRC cohorts taken as a whole. Remarkably however NcirDNA levels were significantly higher in healthy men as compared to women (n = 99, P = 0.010). Men and women did not differ in McirDNA levels. NcirDNA levels increased slightly with age in healthy women, suggesting a potential influence of menopause. A highly significant statistical difference was found between mCRC patients and healthy individuals for NcirDNA (P < 0.0001) and McirDNA (P = 0.019). In healthy volunteers, there was a higher level of NcirDNA at 9:00 AM with no food intake.

Conclusions

Nuclear and mitochondrial cirDNA levels do not vary in the same way with regards to blood stability, collection time, and pathological status. Our observations, of pre-analytical, analytical and demographical factors, could serve to set standard operating procedures and to transpose cirDNA analysis into clinical practice in oncology. Guidelines on the preanalytical conditions will be also presented from data from this study and a complete review of the literature.

Clinical trial identification

Legal entity responsible for the study

Alain R. Thierry.

Funding

SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553.

Editorial Acknowledgement

We are grateful to A. Bauer and B. Ottolini for their help. We would like to thank the clinical investigators from the Kplex2 study: J.L. Raoul, R. Guimbaud, D. Pezet, P. Artru, E. Assenat, C. Borg, M. Mathonnet, C. De La Fouchardière, O. Bouché, and C. Gavoille for collecting the blood samples. The authors would like to thank Kevin Billings and Streck for providing the Cell-Free DNA BCT CE tubes. This work was supported by the INSERM (Institut National de la Santé et de la Recherche Médicale), Lilly (France), and the SIRIC Montpellier Grant (INCa_Inserm_DGOS_12553), France.

Disclosure

All authors have declared no conflicts of interest.

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