Περίληψη:
Circulating tumor DNA (ctDNA) is emerging as a key potential biomarker
for post-diagnosis surveillance but it may also play a crucial role in
the detection of pre-clinical cancer. Small-cell lung cancer (SCLC) is
an excellent candidate for early detection given there are no successful
therapeutic options for late-stage disease, and it displays almost
universal inactivation of TP53. We assessed the presence of TP53
mutations in the cell-free DNA (cfDNA) extracted from the plasma of 51
SCLC cases and 123 non-cancer controls. We identified mutations using a
pipeline specifically designed to accurately detect variants at very low
fractions. We detected TP53 mutations in the cfDNA of 49% SCLC patients
and 11.4% of non-cancer controls. When stratifying the 51 initial SCLC
cases by stage, TP53 mutations were detected in the cfDNA of 35.7%
early-stage and 54.1% late-stage SCLC patients. The results in the
controls were further replicated in 10.8% of an independent series of
102 non-cancer controls. The detection of TP53 mutations in 11% of the
225 non-cancer controls suggests that somatic mutations in cfDNA among
individuals without any cancer diagnosis is a common occurrence, and
poses serious challenges for the development of ctDNA screening tests.
(C) 2016 Published by Elsevier B.V.
Συγγραφείς:
Fernandez-Cuesta, Lynnette
Perdomo, Sandra
Avogbe, Patrice H.
and Leblay, Noemie
Delhomme, Tiffany M.
Gaborieau, Valerie and
Abedi-Ardekani, Behnoush
Chanudet, Estelle
Olivier, Magali and
Zaridze, David
Mukeria, Anush
Vilensky, Marta
Holcatova,
Ivana
Polesel, Jerry
Simonato, Lorenzo
Canova, Cristina and
Lagiou, Pagona
Brambilla, Christian
Brambilla, Elisabeth and
Byrnes, Graham
Scelo, Ghislaine
Le Calvez-Kelm, Florence and
Foll, Matthieu
McKay, James D.
Brennan, Paul
