Next-Generation Sequencing and Result Interpretation in Clinical Oncology: Challenges of Personalized Cancer Therapy.
The tools of next-generation sequencing (NGS) technology, such as targeted sequencing of candidate cancer genes and whole-exome and -genome sequencing, coupled with encouraging clinical results based on the use of targeted therapeutics and biomarker-guided clinical trials, are fueling further technological advancements of NGS technology. However, NGS data interpretation is associated with challenges that must be overcome to promote the techniques' effective integration into clinical oncology practice. Specifically, sequencing of a patient's tumor often yields 30-65 somatic variants, but most of these variants are "passenger" mutations that are phenotypically neutral and thus not targetable. Therefore, NGS data must be interpreted by multidisciplinary decision-support teams to determine mutation actionability and identify potential "drivers," so that the treating physician can prioritize what clinical decisions can be pursued in order to provide cancer therapy that is personalized to the patient and his or her unique genome.
Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy.
Yekaterina B
YB
Khotskaya
Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy.|Department of Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030; email: gmills@mdanderson.org.
Gordon B
GB
Mills
Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy.
Kenna R
KR
Mills Shaw
D000066491:Clinical Decision-Making; D004351:Drug Resistance / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D033183:Interdisciplinary Communication; D008495:Medical Oncology; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D010348:Patient Care Team; D057285:Precision Medicine; D017422:Sequence Analysis, DNA / Q000379:methods*; D000073336:Whole Genome Sequencing
decision support; driver mutations; passenger mutations; variant actionability