Gerald Paul Wright1, David W Chesla2, Mathew H Chung3. 1. General Surgery Residency Program, Grand Rapids Medical Education Partners/Michigan State University General Surgery Residency Program, 221 Michigan St, Suite 200A, Grand Rapids, 49503, MI, USA; Department of Surgery, Michigan State University College of Human Medicine, 221 Michigan St, Suite 200A, Grand Rapids, MI, 49503, USA. Electronic address: wrightgp@upmc.edu. 2. Spectrum Health Universal Biorepository, Grand Rapids, MI, USA. 3. General Surgery Residency Program, Grand Rapids Medical Education Partners/Michigan State University General Surgery Residency Program, 221 Michigan St, Suite 200A, Grand Rapids, 49503, MI, USA; Department of Surgery, Michigan State University College of Human Medicine, 221 Michigan St, Suite 200A, Grand Rapids, MI, 49503, USA; Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, MI, USA.
Abstract
BACKGROUND: Genomic sequencing technology may identify personalized treatment options for patients with pancreatic adenocarcinoma. METHODS: The study was conducted using tissue specimens obtained from 2012 to 2014. Patients with resected pancreatic adenocarcinoma were identified. Next-generation sequencing was performed from paraffin-tumor blocks. Mutational profiles were reviewed to determine available targeted therapies and clinical trial eligibility. RESULTS: Thirty patients were identified. The incidence of mutations was: Kirsten rat sarcoma viral oncogene homolong (KRAS) = 87%, tumor protein 53 (TP53) = 63%, cyclin-dependent kinase inhibitor 2A (CDKN2A) = 20%, Mothers Against Decapentaplegic Homolog 4 (SMAD4) = 20%, epidermal growth factor receptor (EGFR) = 7%. Multiple mutations were found in 73%. All CDKN2A mutations occurred in male patients (P = .06), and there was a trend toward younger patient age in this group (P = .13). Potential for Federal Drug Administration (FDA)-approved targeted therapies was identified in 8 of 30 (27%). In addition, 29 of 30 (97%) had mutations applicable for ongoing phase I or II clinical trials. CONCLUSIONS: Next-generation sequencing of resected pancreatic adenocarcinoma specimens can determine common genetic mutations and identify patients who may be eligible for off-label use of targeted therapies or clinical trial enrollment.
BACKGROUND: Genomic sequencing technology may identify personalized treatment options for patients with pancreatic adenocarcinoma. METHODS: The study was conducted using tissue specimens obtained from 2012 to 2014. Patients with resected pancreatic adenocarcinoma were identified. Next-generation sequencing was performed from paraffin-tumor blocks. Mutational profiles were reviewed to determine available targeted therapies and clinical trial eligibility. RESULTS: Thirty patients were identified. The incidence of mutations was: Kirsten ratsarcoma viral oncogene homolong (KRAS) = 87%, tumor protein 53 (TP53) = 63%, cyclin-dependent kinase inhibitor 2A (CDKN2A) = 20%, Mothers Against Decapentaplegic Homolog 4 (SMAD4) = 20%, epidermal growth factor receptor (EGFR) = 7%. Multiple mutations were found in 73%. All CDKN2A mutations occurred in male patients (P = .06), and there was a trend toward younger patient age in this group (P = .13). Potential for Federal Drug Administration (FDA)-approved targeted therapies was identified in 8 of 30 (27%). In addition, 29 of 30 (97%) had mutations applicable for ongoing phase I or II clinical trials. CONCLUSIONS: Next-generation sequencing of resected pancreatic adenocarcinoma specimens can determine common genetic mutations and identify patients who may be eligible for off-label use of targeted therapies or clinical trial enrollment.
Authors: Ioannis D Kyrochristos; Georgios K Glantzounis; Demosthenes E Ziogas; Ioannis Gizas; Dimitrios Schizas; Efstathios G Lykoudis; Evangelos Felekouras; Anastasios Machairas; Christos Katsios; Theodoros Liakakos; William C Cho; Dimitrios H Roukos Journal: Int J Mol Sci Date: 2017-01-18 Impact factor: 5.923