TY - JOUR
T1 - Clinical next generation sequencing to identify actionable aberrations in a phase I program
AU - Boland, Genevieve M.
AU - Piha-Paul, Sarina A.
AU - Subbiah, Vivek
AU - Routbort, Mark
AU - Herbrich, Shelley M.
AU - Baggerly, Keith
AU - Patel, Keyur P.
AU - Brusco, Lauren
AU - Horombe, Chacha
AU - Naing, Aung
AU - Fu, Siqing
AU - Hong, David S.
AU - Janku, Filip
AU - Johnson, Amber
AU - Broaddus, Russell
AU - Luthra, Raja
AU - Shaw, Kenna
AU - Mendelsohn, John
AU - Mills, Gordon B.
AU - Meric-Bernstam, Funda
PY - 2015
Y1 - 2015
N2 - Purpose: We determined the frequency of recurrent hotspot mutations in 46 cancer-related genes across tumor histologies in patients with advanced cancer. Methods: We reviewed data from 500 consecutive patients who underwent genomic profiling on an IRB-approved prospective clinical protocol in the Phase I program at the MD Anderson Cancer Center. Archival tumor DNA was tested for 740 hotspot mutations in 46 genes (Ampli-Seq Cancer Panel; Life Technologies, CA). Results: Of the 500 patients, 362 had at least one reported mutation/variant. The most common likely somatic mutations were within TP53 (36%), KRAS (11%), and PIK3CA (9%) genes. Sarcoma (20%) and kidney (30%) had the lowest proportion of likely somatic mutations detected, while pancreas (100%), colorectal (89%), melanoma (86%), and endometrial (75%) had the highest. There was high concordance in 62 patients with paired primary tumors and metastases analyzed. 151 (30%) patients had alterations in potentially actionable genes. 37 tumor types were enrolled; both rare actionable mutations in common tumor types and actionable mutations in rare tumor types were identified. Conclusion: Multiplex testing in the CLIA environment facilitates genomic characterization across multiple tumor lineages and identification of novel opportunities for genotype-driven trials.
AB - Purpose: We determined the frequency of recurrent hotspot mutations in 46 cancer-related genes across tumor histologies in patients with advanced cancer. Methods: We reviewed data from 500 consecutive patients who underwent genomic profiling on an IRB-approved prospective clinical protocol in the Phase I program at the MD Anderson Cancer Center. Archival tumor DNA was tested for 740 hotspot mutations in 46 genes (Ampli-Seq Cancer Panel; Life Technologies, CA). Results: Of the 500 patients, 362 had at least one reported mutation/variant. The most common likely somatic mutations were within TP53 (36%), KRAS (11%), and PIK3CA (9%) genes. Sarcoma (20%) and kidney (30%) had the lowest proportion of likely somatic mutations detected, while pancreas (100%), colorectal (89%), melanoma (86%), and endometrial (75%) had the highest. There was high concordance in 62 patients with paired primary tumors and metastases analyzed. 151 (30%) patients had alterations in potentially actionable genes. 37 tumor types were enrolled; both rare actionable mutations in common tumor types and actionable mutations in rare tumor types were identified. Conclusion: Multiplex testing in the CLIA environment facilitates genomic characterization across multiple tumor lineages and identification of novel opportunities for genotype-driven trials.
KW - Actionable genes
KW - Genomic sequencing
UR - http://www.scopus.com/inward/record.url?scp=84940172694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940172694&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4040
DO - 10.18632/oncotarget.4040
M3 - Article
C2 - 26015395
AN - SCOPUS:84940172694
SN - 1949-2553
VL - 6
SP - 20099
EP - 20110
JO - Oncotarget
JF - Oncotarget
IS - 24
ER -