Research Papers:

Development and validation of a targeted next generation DNA sequencing panel outperforming whole exome sequencing for the identification of clinically relevant genetic variants

Eirwen M. Miller, Nicole E. Patterson, Jenna Marcus Zechmeister, Michal Bejerano-Sagie, Maria Delio, Kunjan Patel, Nivedita Ravi, Wilber Quispe-Tintaya, Alexander Maslov, Nichelle Simmons, Maria Castaldi, Jan Vijg, Rouzan G. Karabakhtsian, John M. Greally, Dennis Y.S. Kuo and Cristina Montagna _

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Oncotarget. 2017; 8:102033-102045. https://doi.org/10.18632/oncotarget.22116

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Eirwen M. Miller2, Nicole E. Patterson1, Jenna Marcus Zechmeister2, Michal Bejerano-Sagie1, Maria Delio1, Kunjan Patel1, Nivedita Ravi1, Wilber Quispe-Tintaya1, Alexander Maslov1, Nichelle Simmons1, Maria Castaldi1, Jan Vijg1, Rouzan G. Karabakhtsian3, John M. Greally1, Dennis Y.S. Kuo2 and Cristina Montagna1

1Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA

2Department of Obstetrics & Gynecology and Women’s Health, Division of Gynecologic Oncology, Montefiore Medical Center, Bronx, NY 10461, USA

3Department of Pathology, Montefiore Medical Center, Bronx, NY 10461, USA

Correspondence to:

Cristina Montagna, email: [email protected]

Keywords: target sequencing; next generation sequencing; endometrial carcinoma; tumor recurrence

Received: July 29, 2017    Accepted: September 08, 2017    Published: October 26, 2017


Next generation sequencing (NGS) technologies have revolutionized our approach to genomic research. The use of whole genome sequencing (WGS), whole exome sequencing (WES), transcriptome profiling, and targeted DNA sequencing has exponentially improved our understanding of the human genome and the genetic complexities underlying malignancy. Yet, WGS and WES clinical applications remain limited due to high costs and the large volume of data generated. When utilized to address biological questions in basic science studies, targeted sequencing panels have proven extremely valuable due to reduced costs and higher sequencing depth. However, the routine application of targeted sequencing to the clinical setting is limited to a few cancer subtypes. Some highly aggressive tumor types, like type 2 endometrial cancer (EC), could greatly benefit from routine genomic analysis using targeted sequencing. To explore the potential utility of a mid size panel (~150 genes) in the clinical setting, we developed and validated a custom panel against WGS, WES, and another commercially available targeted panel. Our results indicate that a mid size custom designed panel is as efficient as WGS and WES in mapping variants of biological and clinical relevance, rendering higher coverage, at a lower cost, with fewer variants of uncertain significance. Because of the much higher sequencing depth that could be achieved, our results demonstrate that targeted sequencing outperformed WGS and WES in the mapping of pathogenic variants in a breast cancer case, as well as a case of mixed serous and high-grade endometrioid EC, the most aggressive EC subtype.

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