Clinical correlates of circulating cell-free DNA tumor fraction.

Clinical correlates of circulating cell-free DNA tumor fraction.

<h4>Background</h4>Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Cl...

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Autores principales: Joerg Bredno, Jafi Lipson, Oliver Venn, Alexander M Aravanis, Arash Jamshidi
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/fc02433213244ffc9d82bfb80a55e61d
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spelling oai:doaj.org-article:fc02433213244ffc9d82bfb80a55e61d2021-12-02T20:19:35ZClinical correlates of circulating cell-free DNA tumor fraction.1932-620310.1371/journal.pone.0256436https://doaj.org/article/fc02433213244ffc9d82bfb80a55e61d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256436https://doaj.org/toc/1932-6203<h4>Background</h4>Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated.<h4>Methods and findings</h4>Circulating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test.<h4>Conclusions</h4>Prognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.Joerg BrednoJafi LipsonOliver VennAlexander M AravanisArash JamshidiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256436 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Joerg Bredno
Jafi Lipson
Oliver Venn
Alexander M Aravanis
Arash Jamshidi
Clinical correlates of circulating cell-free DNA tumor fraction.
description <h4>Background</h4>Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated.<h4>Methods and findings</h4>Circulating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test.<h4>Conclusions</h4>Prognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.
format article
author Joerg Bredno
Jafi Lipson
Oliver Venn
Alexander M Aravanis
Arash Jamshidi
author_facet Joerg Bredno
Jafi Lipson
Oliver Venn
Alexander M Aravanis
Arash Jamshidi
author_sort Joerg Bredno
title Clinical correlates of circulating cell-free DNA tumor fraction.
title_short Clinical correlates of circulating cell-free DNA tumor fraction.
title_full Clinical correlates of circulating cell-free DNA tumor fraction.
title_fullStr Clinical correlates of circulating cell-free DNA tumor fraction.
title_full_unstemmed Clinical correlates of circulating cell-free DNA tumor fraction.
title_sort clinical correlates of circulating cell-free dna tumor fraction.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/fc02433213244ffc9d82bfb80a55e61d
work_keys_str_mv AT joergbredno clinicalcorrelatesofcirculatingcellfreednatumorfraction
AT jafilipson clinicalcorrelatesofcirculatingcellfreednatumorfraction
AT olivervenn clinicalcorrelatesofcirculatingcellfreednatumorfraction
AT alexandermaravanis clinicalcorrelatesofcirculatingcellfreednatumorfraction
AT arashjamshidi clinicalcorrelatesofcirculatingcellfreednatumorfraction
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