Next‐generation sequencing ( NGS ) of tumor tissue (ie, clinical sequencing) can guide clinical management by providing information about actionable gene aberrations that have diagnostic and therapeutic significance. Here, we undertook a hospital‐based prospective study ( TOP ‐ GEAR project, 2nd stage) to investigate the feasibility and utility of NGS ‐based analysis of 114 cancer‐associated genes (the NCC Oncopanel test). We examined 230 cases (comprising more than 30 tumor types) of advanced solid tumors, all of which were matched with nontumor samples. Gene profiling data were obtained for 187 cases (81.3%), 111 (59.4%) of which harbored actionable gene aberrations according to the Clinical Practice Guidelines for Next Generation Sequencing in Cancer Diagnosis and Treatment (Edition 1.0) issued by 3 major Japanese cancer‐related societies. Twenty‐five (13.3%) cases have since received molecular‐targeted therapy according to their gene aberrations. These results indicate the utility of tumor‐profiling multiplex gene panel testing in a clinical setting in Japan. This study is registered with UMIN Clinical Trials Registry ( UMIN 000011141).

Background: To improve the prognosis of patients with pancreatic cancer, more accurate serum diagnostic methods are required. We used serum metabolomics as a diagnostic method for pancreatic cancer.Methods: Sera from patients with pancreatic cancer, healthy volunteers, and chronic pancreatitis were collected at multiple institutions. The pancreatic cancer and healthy volunteers were randomly allocated to the training or the validation set. All of the chronic pancreatitis cases were included in the validation set. In each study, the subjects' serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS) and a data processing system using an in-house library. The diagnostic model constructed via multiple logistic regression analysis in the training set study was evaluated on the basis of its sensitivity and specificity, and the results were confirmed by the validation set study.Results: In the training set study, which included 43 patients with pancreatic cancer and 42 healthy volunteers, the model possessed high sensitivity (86.0%) and specificity (88.1%) for pancreatic cancer. The use of the model was confirmed in the validation set study, which included 42 pancreatic cancer, 41 healthy volunteers, and 23 chronic pancreatitis; that is, it displayed high sensitivity (71.4%) and specificity (78.1%); and furthermore, it displayed higher sensitivity (77.8%) in resectable pancreatic cancer and lower false-positive rate (17.4%) in chronic pancreatitis than conventional markers.Conclusions: Our model possessed higher accuracy than conventional tumor markers at detecting the resectable patients with pancreatic cancer in cohort including patients with chronic pancreatitis.Impact: It is a promising method for improving the prognosis of pancreatic cancer via its early detection and accurate discrimination from chronic pancreatitis. Cancer Epidemiol Biomarkers Prev; 22(4); 571-9. Ó2013 AACR.

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Epidermal growth factor receptor (EGFR) mutations are a strong determinant of tumor response to gefitinib in non-small cell lung cancer (NSCLC). We attempted to elucidate the feasibility of EGFR mutation detection in cells of pleural effusion fluid. We obtained 24 samples of pleural effusion fluid from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were used for detection. EGFR mutation status was determined by a direct sequencing method (exons 18-21) and by the Scorpion Amplified Refractory Mutation System (ARMS) method. EGFR mutations were detected in eight cases. Three mutations were detected by both methods, and the other five mutations were detected by Scorpion ARMS alone. The mutations were detected by both methods in all four partial responders among the seven patients who received gefitinib therapy. Direct sequencing detected the mutations in only two of four cases with partial response. These results suggest that the DNA in pleural effusion fluid can be used to detect EGFR mutations. The Scorpion ARMS method appears to be more sensitive for detecting EGFR mutations than the direct sequencing method. (Cancer Sci 2006; 97: 642-648) L ung cancer is a major cause of cancer-related mortality worldwide and is expected to remain a major health problem for the foreseeable future.(1) Targeting the epidermal growth factor receptor (EGFR) is one appealing strategy for the treatment of non-small cell lung cancer (NSCLC), because EGFR has been found to be expressed, sometimes strongly, in NSCLC.(2) Mutations of EGFR tyrosine kinase in NSCLC and hyper-responsiveness to gefitinib, a selective EGFR tyrosine kinase inhibitor, have been reported. (3,4) These mutations consist of small in-frame deletions or substitutions clustered around the ATP-binding site in exons 18, 19 and 21 of EGFR, and increase the affinity of the enzyme for ATP and gefitinib. Some investigators have subsequently found that EGFR mutations are a strong determinant of tumor response to EGFR tyrosine kinase inhibitor.(5-7) Approximately 90% of the NSCLC-associated EGFR mutations in two reports consisted of two major EGFR mutations (E746_A750del in exon 19 and L858R in exon 21). (5,8) These investigators used surgical tissue to detect the EGFR mutations in their trials. As it is often difficult to obtain a tumor sample from patients with inoperable NSCLC, a method of detecting mutant EGFR, especially the two major mutations, in other specimens needs to be established.Malignant pleural effusion is a common complication of lung cancer and is present in approximately 15% of lung cancer patients (9) and in 10-50% of patients at the time of diagnosis.Approximately one-half of NSCLC patients with pleural effusion are initially positive cytologically, and most of the effusions are ultimately determined to be malignant. As sampling of pleural effusion fluid is usually easy, non-invasive and repeatable, we hypothesized that tumor cells in the pleural effusion fluid of NSCLC patients are a source of useful infor...