BACKGROUND:
Prompted by the revolution in high-throughput sequencing and its potential impact for treating cancer patients, we initiated a clinical research study to compare the ability of different sequencing assays and analysis methods to analyze glioblastoma tumors and generate real-time potential treatment options for physicians.
METHODS:
A consortium of seven institutions in New York City enrolled 30 patients with glioblastoma and performed tumor whole genome sequencing (WGS) and RNA sequencing (RNA-seq; collectively WGS/RNA-seq); 20 of these patients were also analyzed with independent targeted panel sequencing. We also compared results of expert manual annotations with those from an automated annotation system, Watson Genomic Analysis (WGA), to assess the reliability and time required to identify potentially relevant pharmacologic interventions.
RESULTS:
WGS/RNAseq identified more potentially actionable clinical results than targeted panels in 90% of cases, with an average of 16-fold more unique potentially actionable variants identified per individual; 84 clinically actionable calls were made using WGS/RNA-seq that were not identified by panels. Expert annotation and WGA had good agreement on identifying variants [mean sensitivity = 0.71, SD = 0.18 and positive predictive value (PPV) = 0.80, SD = 0.20] and drug targets when the same variants were called (mean sensitivity = 0.74, SD = 0.34 and PPV = 0.79, SD = 0.23) across patients. Clinicians used the information to modify their treatment plan 10% of the time.
CONCLUSION:
These results present the first comprehensive comparison of technical and machine augmented analysis of targeted panel and WGS/RNA-seq to identify potential cancer treatments.
BMC Med Genomics. 2019 Apr 25;12(1):56. doi: 10.1186/s12920-019-0500-0.
Frank MO1,2, Koyama T3, Rhrissorrakrai K3, Robine N1, Utro F3, Emde AK1, Chen BJ1,4, Arora K1, Shah M1, Geiger H1, Felice V1, Dikoglu E1,5, Rahman S1, Fang A1, Vacic V1,6, Bergmann EA1,7, Vogel JLM1,2,8, Reeves C1, Khaira D1, Calabro A1,9, Kim D1, Lamendola-Essel MF1,10, Esteves C1,11, Agius P1, Stolte C1, Boockvar J12, Demopoulos A13, Placantonakis DG14, Golfinos JG14, Brennan C15, Bruce J16, Lassman AB16, Canoll P16, Grommes C15, Daras M15, Diamond E15, Omuro A15,17, Pentsova E15, Orange DE2,18, Harvey SJ19, Posner JB15, Michelini VV19, Jobanputra V1,16, Zody MC1, Kelly J3, Parida L3, Wrzeszczynski KO1, Royyuru AK3, Darnell RB20,21,22.
Author information
1 New York Genome Center, 101 Avenue of the Americas, New York, NY, 10013, USA.
2 Laboratory of Molecular Neuro-Oncology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
3 IBM Thomas J. Watson Research Center, Yorktown Heights, NY, 10598, USA.
4 Present address: Google, 76 9th Avenue, New York, NY, 10011, USA.
5 Present address: Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
6 Present address: 23&Me, 899 W Evelyn Ave, Mountain View, CA, 94041, USA.
7 Present address: Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51 D-79108, Freiburg, Germany.
8 Present address: The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
9 Present address: The Tisch Cancer Institute, 1470 Madison Avenue, New York, NY, 10029, USA.
10 Present address: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
11 Present address: Harvard Medical School, 10 Shattuck Street, Boston, MA, 02115, USA.
12 Northwell Health, Lenox Hill Hospital, 100 E. 77th Street, New York, NY, 10075, USA.
13 Northwell Health, The Brain Tumor Center, 450 Lakeville Road, Lake Success, Lakeville, NY, 11042, USA.
14 New York University, School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
15 Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
16 Columbia University Medical Center, 710 West 168th Street, New York, NY, 10032, USA.
17 Present address: Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.
18 Hospital for Special Surgery, 535 E. 70th Street, New York, NY, 10021, USA.
19 IBM Watson Health, NW Broken Sound Bkwy, Boca Raton, FL, 33487, USA.
20 New York Genome Center, 101 Avenue of the Americas, New York, NY, 10013, USA. darnelr@rockefeller.edu.
21 Laboratory of Molecular Neuro-Oncology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. darnelr@rockefeller.edu.
22 Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
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