First name
Angela
Middle name
J
Last name
Waanders

Title

Development and Clinical Validation of a Large Fusion Gene Panel for Pediatric Cancers.

Year of Publication

2019

Number of Pages

Date Published

2019 Jun 27

ISSN Number

1943-7811

Abstract

<p>Gene fusions are one of the most common genomic alterations in pediatric cancer. Many fusions encode oncogenic drivers and play important roles in cancer diagnosis, risk stratification, and treatment selection. We report the development and clinical validation of a large custom-designed RNA sequencing panel, CHOP Fusion panel, using anchored multiplex PCR technology. The panel interrogates 106 cancer genes known to be involved in nearly 600 different fusions reported in hematological malignancies and solid tumors. The panel works well with different types of samples including formalin-fixed, paraffin-embedded samples. The panel demonstrated excellent analytic accuracy with 100% sensitivity and specificity on 60 pediatric tumor validation samples. In addition to identifying all known fusions in the validation samples, three unrecognized yet clinically significant fusions were also detected. Two-hundred and sevety-six clinical cases were analyzed after the validation and 51 different fusions were identified in 104 cases. Of these, 16 fusions were not previously reported at the time of discovery. These fusions provided genomic information useful for clinical management. Our experience demonstrates that CHOP Fusion panel can detect the vast majority of known and certain novel clinically relevant fusion genes in pediatric cancers accurately, efficiently, and cost effectively, and provides an excellent tool for new fusion gene discovery.</p>

DOI

10.1016/j.jmoldx.2019.05.006

Alternate Title

J Mol Diagn

PMID

31255796
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Title

Clinical utility of custom-designed NGS panel testing in pediatric tumors.

Year of Publication

2019

Number of Pages

32

Date Published

2019 May 28

ISSN Number

1756-994X

Abstract

<p><strong>BACKGROUND: </strong>Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, the standard approach was single-gene or focused multigene testing, but many centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report the laboratory validation and clinical utility of a large cohort of clinical NGS somatic sequencing results in diagnosis, prognosis, and treatment of a wide range of pediatric cancers.</p>

<p><strong>METHODS: </strong>Subjects were accrued retrospectively at a single pediatric quaternary-care hospital. Sequence analyses were performed on 367 pediatric cancer samples using custom-designed NGS panels over a 15-month period. Cases were profiled for mutations, copy number variations, and fusions identified through sequencing, and their clinical impact on diagnosis, prognosis, and therapy was assessed.</p>

<p><strong>RESULTS: </strong>NGS panel testing was incorporated meaningfully into clinical care in 88.7% of leukemia/lymphomas, 90.6% of central nervous system (CNS) tumors, and 62.6% of non-CNS solid tumors included in this cohort. A change in diagnosis as a result of testing occurred in 3.3% of cases. Additionally, 19.4% of all patients had variants requiring further evaluation for potential germline alteration.</p>

<p><strong>CONCLUSIONS: </strong>Use of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients.</p>

DOI

10.1186/s13073-019-0644-8

Alternate Title

Genome Med

PMID

31133068
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