Noninvasive Molecular Detection of Cancer - the Bench and the Bedside

Abstract

The more profound understanding of the genetics and molecular pathways driving human tumorigenesis is paralleled by an ongoing interest to translate this knowledge into development of cancer biomarkers, termed molecular tumor markers. The molecular changes observed in tumors frequently constitute early events which are detectable as signatures of malignancy in body fluids and their occurrence may precede clinical cancer diagnosis. Thus, beyond applicability on tissue samples, molecular markers for tumor signatures should allow noninvasive or minimally invasive diagnosis in blood and/or other body fluid samples. However, to qualify as a clinically useful molecular tumor marker for initial diagnosis and detection of recurrent disease, a molecular tumor marker must have better test characteristics (sensitivity, specifity) than currently applied tumor markers. A molecular tumor marker should also be suitable for screening purposes by defining the subset of individuals for which definite cancer diagnosis by more invasive and/or expensive additional investigations is indicated. In addition, there is a demand for molecular tumor markers to be used as reliable surrogate endpoints in cancer prevention trials. Recommendation for the use of individual molecular tumor markers within evidence-based medicine criteria should ideally be derived from their overall efficacy to reduce tumor-specific mortality. This review focuses on DNA based, RNA based and proteomics based molecular methods of noninvasive cancer detection in bodily fluids and assess the value of these methods for the current and future clinical management of cancer patients.

The prognostic value of circulating plasma DNA level and its allelic imbalance on chromosome 8p in patients with hepatocellular carcinoma

“…On the other hand, in some other patients, the AI was detected in circulating plasma DNA but not in HCC tissue, and the possible reason may be due to the heterogeneity of tumor cells; only some of them had microsatellite polymorphisms, and the circulating DNA was mainly released by the micrometastatic tumor cells with AI but not primary tumor (Lin et al 2002;Dahse et al 2002;Utting et al 2002). Another explanation is the clones with polymorphism were ruined precedently, and could be detected only in circulating DNA (Goessl 2003;Sozzi et al 1999).…”

Detailed Technical Analysis of Urine RNA-Based Tumor Diagnostics Reveals ETS2/Urokinase Plasminogen Activator to Be a Novel Marker for Bladder Cancer

“…The T7-transcript was prepared from a purified EcoRV-restricted pet24a(ϩ) vector (Promega) fragment containing the Photinus pyralis luciferase gene. The reaction mixture (50 L) for T7 transcription contained 1ϫ reaction buffer (MBI Fermentas), 2 mmol/L each nucleotide triphosphate, 40 units RNase inhibitor (Ambion), 30 units T7 6 Human genes: hTERT, human telomerase reverse transcriptase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; RPLP0, ribosomal protein, large, P0; UBC, ubiquitin C; ETS2, v-ets erythroblastosis virus E26 oncogene homolog 2 (avian); uPA, urokinase plasminogen activator; HTATIP2, HIV-1 Tat interactive protein 2, 30kDa; UPK1A, uroplakin 1A. Urine was collected from 139 participants.…”

“…Despite these obstacles, the detection of RNA tumor markers in urine has been reported as an emerging tool for noninvasive tumor diagnosis (6 ). One of the most frequently studied markers for bladder cancer is the mRNA of human telomerase reverse transcriptase (hTERT), 6 because its concentration correlates with telomerase activity, which is absent in most human somatic cells but detectable in 85% of human tumors (7 ).…”

“…One of the most frequently studied markers for bladder cancer is the mRNA of human telomerase reverse transcriptase (hTERT), 6 because its concentration correlates with telomerase activity, which is absent in most human somatic cells but detectable in 85% of human tumors (7 ). RNA extracts from tumor material (8)(9)(10), bladder washings (11,12 ), and exfoliated cells (13 ) have been used for RT-qPCR-based hTERT mRNA quantification for the detection of bladder cancer, resulting in reported diagnostic sensitivities of 50% to 100%.…”

Heat shock protein 60 and chromatin assembly factor-1 mRNA levels in hepatitis C virus-related hepatocellular carcinoma and clinical significance

“…13 The detection of RNA tumor markers in urine has been reported as an emerging tool for noninvasive tumor diagnosis. 14 Aim of the work was to clarify the role of HSP60 and CAF-1 mRNA gene expression in blood and urine in diagnosis of HCV-related HCC.…”