11% mutation frequency of TP53 in non-cancer samples

Tlexander

Very interesting: Why there are TP53 mutation in non-cancer samples? Really feel surprising??' `( {2 D; |7 J5 j
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http://www.ncbi.nlm.nih.gov/pubmed/27377626
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/ m* A3 q! E+ d  j# \: xIdentification of Circulating Tumor DNA for the Early Detection of Small-cell Lung Cancer.1 p- m, Z( u& `8 k0 W

, d' r1 _8 j6 W6 \: _& p  [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.