Maxim B Freidin1, Dasha V Freydina1, Maria Leung2, Angeles Montero Fernandez2, Andrew G Nicholson1, Eric Lim3. 1. Royal Brompton and Harefield National Health Service Foundation Trust, London, UK; National Heart and Lung Institute, Imperial College London, London, UK. 2. Royal Brompton and Harefield National Health Service Foundation Trust, London, UK; 3. Royal Brompton and Harefield National Health Service Foundation Trust, London, UK; National Heart and Lung Institute, Imperial College London, London, UK. e.lim@rbht.nhs.uk.
Abstract
BACKGROUND: Circulating biomarkers, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are both considered for blood-based mutation detection, but limited studies have compared them in a head-to-head manner. Using KRAS (Kirsten rat sarcoma viral oncogene homolog), we performed such a comparison in patients who underwent surgery for suspected lung cancer. METHODS: We recruited 93 patients, including 82 with lung cancer and 11 with benign diseases of the lung. Mutations were detected in codons 12 and 13 of KRAS in DNA extracted from CTCs, plasma, and matched tumors or lung tissues with custom-designed coamplification at lower denaturation temperature (COLD)-PCR assays, high-resolution melt analysis (HRM), and commercial assays (Roche Cobas(®) KRAS mutation test and Qiagen Therascreen(®) pyrosequencing KRAS kit). RESULTS: With the Cobas mutation test, we identified KRAS mutations in 21.3% of tumors. Mutation analysis in matched CTC DNA and ctDNA samples by COLD-PCR/HRM assay revealed mutations in 30.5% (ctDNA) and 23.2% (CTC DNA) of patients with lung cancer. Combined results of different tests revealed KRAS-positive cases for 28% of tumors. The diagnostic sensitivity and specificity of KRAS mutation detection in tumors achieved with ctDNA was 0.96 (95% CI 0.81-1.00) and 0.95 (0.85-0.99), respectively. The diagnostic test performance was lower for CTC DNA, at 0.52 (0.34-0.73) and 0.88 (0.79-0.95). CONCLUSIONS: Our results support ctDNA as a preferential specimen type for mutation screening in thoracic malignancies vs CTC DNA, achieving greater mutation detection than either CTCs or limited amounts of tumor tissue alone.
BACKGROUND: Circulating biomarkers, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are both considered for blood-based mutation detection, but limited studies have compared them in a head-to-head manner. Using KRAS (Kirsten ratsarcoma viral oncogene homolog), we performed such a comparison in patients who underwent surgery for suspected lung cancer. METHODS: We recruited 93 patients, including 82 with lung cancer and 11 with benign diseases of the lung. Mutations were detected in codons 12 and 13 of KRAS in DNA extracted from CTCs, plasma, and matched tumors or lung tissues with custom-designed coamplification at lower denaturation temperature (COLD)-PCR assays, high-resolution melt analysis (HRM), and commercial assays (Roche Cobas(®) KRAS mutation test and Qiagen Therascreen(®) pyrosequencing KRAS kit). RESULTS: With the Cobas mutation test, we identified KRAS mutations in 21.3% of tumors. Mutation analysis in matched CTC DNA and ctDNA samples by COLD-PCR/HRM assay revealed mutations in 30.5% (ctDNA) and 23.2% (CTC DNA) of patients with lung cancer. Combined results of different tests revealed KRAS-positive cases for 28% of tumors. The diagnostic sensitivity and specificity of KRAS mutation detection in tumors achieved with ctDNA was 0.96 (95% CI 0.81-1.00) and 0.95 (0.85-0.99), respectively. The diagnostic test performance was lower for CTC DNA, at 0.52 (0.34-0.73) and 0.88 (0.79-0.95). CONCLUSIONS: Our results support ctDNA as a preferential specimen type for mutation screening in thoracic malignancies vs CTC DNA, achieving greater mutation detection than either CTCs or limited amounts of tumor tissue alone.
Authors: Dimple Y Chudasama; Daria V Freydina; Maxim B Freidin; Maria Leung; Angeles Montero Fernandez; Alexandra Rice; Andrew G Nicholson; Emmanouil Karteris; Vladimir Anikin; Eric Lim Journal: Ann Transl Med Date: 2016-12
Authors: Marija Debeljak; Michael Noë; Stacy L Riel; Lisa M Haley; Alexis L Norris; Derek A Anderson; Emily M Adams; Masaya Suenaga; Katie F Beierl; Ming-Tseh Lin; Michael G Goggins; Christopher D Gocke; James R Eshleman Journal: Mol Diagn Ther Date: 2018-10 Impact factor: 4.074
Authors: M Cabanero; R Sangha; B S Sheffield; M Sukhai; M Pakkal; S Kamel-Reid; A Karsan; D Ionescu; R A Juergens; C Butts; M S Tsao Journal: Curr Oncol Date: 2017-04-27 Impact factor: 3.677