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.
- MeSH
- časná detekce nádoru MeSH
- DNA nádorová * krev MeSH
- leukocyty metabolismus MeSH
- lidé MeSH
- malobuněčný karcinom plic krev diagnóza genetika MeSH
- mutace MeSH
- nádorové biomarkery * MeSH
- nádorový supresorový protein p53 genetika MeSH
- nádory plic krev diagnóza genetika MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Malobuněčný plicní karcinom (SCLC) představuje cca 20-25 % plicních karcinomů. Vyznačuje se typickým histologickým nálezem, agresivním rychlým růstem a časným metastázováním. V časných stadiích je však velmi dobře citlivý na chemo- a radioterapii, proto je zvláště u tohoto typu plicního nádoru důležitá časná diagnostika. ProGRP je relativně nový marker pro diagnostiku, diferenciální diagnostiku a sledování SCLC, dle literatury se senzitivitou a specificitou vyšší než dosud používané markery, tj. NSE a CEA. Je prezentováno srovnání hodnot proGRP u pacientů s prokázaným SCLC a jinými diagnózami včetně karcinoidu, srovnání podle klinických stadií SCLC a srovnání s NSE, která je v praxi nejvíce používaným nádorovým markerem pro SCLC.
Small-cell lung cancer (SCLC) accounts for 20-25% of all lung cancers. The typical clinical picture includes histological findings, aggressive growth and early metastases. In its early stages, however, SCLC is very sensitive to chemo- and radiotherapy. Therefore, early diagnosis is very important in this type of lung cancer. ProGRP Is a relatively new marker for the diagnosis, differential diagnosis and monitoring of SCLC. Its sensitivity and specificity were reported to be higher than those of the classical markers, NSE and CEA. A comparison of proGRP values in patients with confirmed SCLC and other diagnoses including carcinoid is presented. ProGRP values are compared in both clinical stages (limited and extended disease) and set against NSE, the most commonly used marker in routine practice.
