Journal
ONCOTARGET
Volume 6, Issue 24, Pages 20099-20110Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4040
Keywords
genomic sequencing; actionable genes
Categories
Funding
- Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer Therapy
- NCI [5T32CA009599, 1U01 CA180964]
- NCATS [UL1 TR000371]
- Nellie B. Connally Breast Cancer Research Endowment
- Bosarge Family Foundation
- MD Anderson Cancer Center [P30 CA016672]
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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.
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