ABSTRACT
PURPOSE: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST.MATERIALS AND METHODS: Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs.RESULTS: Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications.CONCLUSIONS: Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.
ABSTRACT
BACKGROUND: Liquid-based cytology is currently known as an effective method, and cervical cytology has been shown to be especially effective from of malignancy detection. In our study, the cytological detection rates of the Thinprep (Liquid-based cytology) and conventional cytology (bronchial washing & brushing) for endobronchial lesions were compared. METHODS: Between July 2005 and September 2005, the data from 30 patients with respiration symptom, who had shown abnormal lesion on bronchoscopy, were collected. RESULTS: The bronchoscopic biopsy group was consisted of 30 cytodiagnosis specimens, 24 of which were confirmed to be malignant. The others were tuberculosis (4), bronchiectasis and bronchopulmonary fistula (1 each). Of the 24 malignant case, cancer or atypical cells were detected in 19, 17 and 12 of the Thinprep, brushing cytology and washing cytology cases, respectively. None one of the methods detected cancer cells in the non-malignant specimens. Washing cytology has shown sensitivity, specificity, and positive and negative predictive values of 50, 100, 100 and 33.3% respectively. Brushing cytology has shown sensitivity, specificity, and positive and negative predictive values of 70.8, 100, 100 and 46.2%, respectively. Thinprep has shown sensitivity, specificity, and positive and negative predictive values of 79.2, 100, 100 and 54%, respectively. CONCLUSIONS: Thinprep (liquid-based cytology) showed better sensitivity and negative predictive values for the evaluation of lung cancer than conventional cytology. However a large-scale study will be needed in the future.