Improving the performance of somatic mutation identification by recovering circulating tumor DNA mutations

Yu Fu; Cécile Jovelet; Thomas Filleron; Marion Pedrero; Nelly Motté; Yannick Boursin; Yufei Luo; Christophe Massard; Mario Campone; Christelle Levy; Véronique Diéras; Thomas Bachelot; Julie Garrabey; Jean Charles Soria; Ludovic Lacroix; Fabrice André; Celine Lefebvre

doi:10.1158/0008-5472.CAN-15-3457

Improving the performance of somatic mutation identification by recovering circulating tumor DNA mutations

Yu Fu, Cécile Jovelet, Thomas Filleron, Marion Pedrero, Nelly Motté, Yannick Boursin, Yufei Luo, Christophe Massard, Mario Campone, Christelle Levy, Véronique Diéras, Thomas Bachelot, Julie Garrabey, Jean Charles Soria, Ludovic Lacroix, Fabrice André, Celine Lefebvre

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13 Citations (Scopus)

Abstract

DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53. We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell-free tumor DNA by plasma analyses (n = 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls.

Original language	English
Pages (from-to)	5954-5961
Number of pages	8
Journal	Cancer Research
Volume	76
Issue number	20
DOIs	https://doi.org/10.1158/0008-5472.CAN-15-3457
Publication status	Published - 15 Oct 2016

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10.1158/0008-5472.CAN-15-3457

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Fu, Y., Jovelet, C., Filleron, T., Pedrero, M., Motté, N., Boursin, Y., Luo, Y., Massard, C., Campone, M., Levy, C., Diéras, V., Bachelot, T., Garrabey, J., Soria, J. C., Lacroix, L., André, F., & Lefebvre, C. (2016). Improving the performance of somatic mutation identification by recovering circulating tumor DNA mutations. Cancer Research, 76(20), 5954-5961. https://doi.org/10.1158/0008-5472.CAN-15-3457

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title = "Improving the performance of somatic mutation identification by recovering circulating tumor DNA mutations",

abstract = "DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53. We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell-free tumor DNA by plasma analyses (n = 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls.",

author = "Yu Fu and C{\'e}cile Jovelet and Thomas Filleron and Marion Pedrero and Nelly Mott{\'e} and Yannick Boursin and Yufei Luo and Christophe Massard and Mario Campone and Christelle Levy and V{\'e}ronique Di{\'e}ras and Thomas Bachelot and Julie Garrabey and Soria, {Jean Charles} and Ludovic Lacroix and Fabrice Andr{\'e} and Celine Lefebvre",

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Fu, Y, Jovelet, C, Filleron, T, Pedrero, M, Motté, N, Boursin, Y, Luo, Y, Massard, C, Campone, M, Levy, C, Diéras, V, Bachelot, T, Garrabey, J, Soria, JC, Lacroix, L, André, F & Lefebvre, C 2016, 'Improving the performance of somatic mutation identification by recovering circulating tumor DNA mutations', Cancer Research, vol. 76, no. 20, pp. 5954-5961. https://doi.org/10.1158/0008-5472.CAN-15-3457

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T1 - Improving the performance of somatic mutation identification by recovering circulating tumor DNA mutations

AU - Fu, Yu

AU - Jovelet, Cécile

AU - Filleron, Thomas

AU - Pedrero, Marion

AU - Motté, Nelly

AU - Boursin, Yannick

AU - Luo, Yufei

AU - Massard, Christophe

AU - Campone, Mario

AU - Levy, Christelle

AU - Diéras, Véronique

AU - Bachelot, Thomas

AU - Garrabey, Julie

AU - Soria, Jean Charles

AU - Lacroix, Ludovic

AU - André, Fabrice

AU - Lefebvre, Celine

PY - 2016/10/15

Y1 - 2016/10/15

N2 - DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53. We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell-free tumor DNA by plasma analyses (n = 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls.

AB - DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53. We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell-free tumor DNA by plasma analyses (n = 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls.

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Improving the performance of somatic mutation identification by recovering circulating tumor DNA mutations

Abstract

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