| Autor: |
Kaur P; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, United States.; University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, United States., Porras TB; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, United States.; University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, United States., Ring A; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, United States.; University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, United States., Carpten JD; University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, United States.; Department of Translational Genomics, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, United States., Lang JE; Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, United States. julie.lang@med.usc.edu.; University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, United States. julie.lang@med.usc.edu. |
| Abstrakt: |
Whole exome sequencing (WES), targeted gene panel sequencing and single nucleotide polymorphism (SNP) arrays are increasingly used for the identification of actionable alterations that are critical to cancer care. Here, we compared The Cancer Genome Atlas (TCGA) and the Genomics Evidence Neoplasia Information Exchange (GENIE) breast cancer genomic datasets (array and next generation sequencing (NGS) data) in detecting genomic alterations in clinically relevant genes. We performed an in silico analysis to determine the concordance in the frequencies of actionable mutations and copy number alterations/aberrations (CNAs) in the two most common breast cancer histologies, invasive lobular and invasive ductal carcinoma. We found that targeted sequencing identified a larger number of mutational hotspots and clinically significant amplifications that would have been missed by WES and SNP arrays in many actionable genes such as PIK3CA, EGFR, AKT3, FGFR1, ERBB2, ERBB3 and ESR1. The striking differences between the number of mutational hotspots and CNAs generated from these platforms highlight a number of factors that should be considered in the interpretation of array and NGS-based genomic data for precision medicine. Targeted panel sequencing was preferable to WES to define the full spectrum of somatic mutations present in a tumor. |
