In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 214-214
Abstract:
214 Background: GB Ca is the leading cause of cancer mortality in Chilean women and its incidence is high in Southeast Asia. Molecular characterization of this disease is limited to small retrospective studies of prognostic biomarkers. Methods: 54 surgically resected GB Ca cases were selected. DNA was extracted from microdissected tumors; genetic mutations analyzed using two platforms a) Sequenom MassARRAY, a mass spectrometry-based approach for 90 targetable mutations including PIK3CA, KRAS, EGFR, FGFR, CTNNB1, MET, ALK and AKT and b) Exome sequencing using the Illumina HiSeq2000 sequencer for novel genetic variants in the coding regions. Sample preparation followed the standard Agilent SureSelect XT protocol with the 71Mb +UTR capture library. A stepwise filtering approach was used to identify variants by screening for nonsynonymous substitutions, comparison of exomes to matched control and dbSNP database to exclude common variants. Variants not predicted to affect protein function were excluded. KM survival curves and log rank test were used to correlate genotyping results with survival. Results: 46 cases were selected for Sequenom MassARRAY and whole exome sequencing performed on 8 cases and control non-tumor tissue. Sequenom identified mutations in KRAS (3 cases), IDH1 (4), ALK1 (1), MET (1), NRAS (3) and PIK3CA genes (2). Overall survival was poorer in KRAS [24 vs. 75 weeks, p=0.008] and IDH1 [27 vs. 80 weeks, p=0.0008] mutation carriers. Exome sequencing after filtering revealed genetic variants in 6 cases with an overall low mutation rate. There were no overlapping mutations and we identified 45 functional mutations in STK11, CDKN2A, IKZF3, GRM6, TP53 and CTNNB1 genes, known to be prognostic in other cancers. ABCB1 transporter, TP53 and STK11mutations were predicted to have high functional impact. Ingenuity pathway analysis identified p53, WNT/ ß-catenin, GBM and thyroid cancer signaling and cell cycle regulation to be the top hits. Conclusions: This first high-throughput genomic screening of GB Ca using different platforms identifies known and unique variants in cancer genes. Sequencing of additional cases and efforts to develop a GB Ca-specific somatic mutation panel are ongoing.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.4_suppl.214
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
