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Next‐Generation Sequencing for Patients with Sarcoma: A Single Center Experience
Background Sarcomas comprise over 50 subtypes of mesenchymal cancers. For the majority of sarcomas, the driver mutations remain unknown. In this article, we describe our experience with a targeted next‐generation sequencing (NGS) platform in clinic patients. Materials and Methods We retrospectively...
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Published in: | The oncologist (Dayton, Ohio) Ohio), 2018-02, Vol.23 (2), p.234-242 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background
Sarcomas comprise over 50 subtypes of mesenchymal cancers. For the majority of sarcomas, the driver mutations remain unknown. In this article, we describe our experience with a targeted next‐generation sequencing (NGS) platform in clinic patients.
Materials and Methods
We retrospectively analyzed results of NGS using 133 tumor samples from patients diagnosed with a variety of sarcomas that were analyzed with targeted NGS covering over 400 cancer‐related genes (405 DNA, 265 RNA) on a commercially available platform.
Results
An average of two gene alterations were identified per tumor sample (range 0–14), and a total of 342 DNA mutations were detected. Eight‐eight percent of samples had at least one detected mutation. The most common mutations were in the cell cycle, including TP53 (n = 35), CDKN2A/B (n = 23), and RB1 (n = 19). Twenty‐seven PI3‐kinase pathway alterations were observed, including PTEN (n = 14), PIK3Ca (n = 4), TSC1 (n = 1), TSC2 (n = 3), STK11 (n = 1), mTOR (n = 3), and RICTOR (n = 2). There were 75 mutations in genes that are targetable with existing drugs (excluding KIT in gastrointestinal stromal tumor) that would allow enrollment onto clinical trials. In general, the estimated tumor mutation burden was low, in particular for those with disease‐defining gene fusions or genetic alterations. Microsatellite instability (MSI) data were available for 50 patients, and all were MSI stable.
Conclusion
Our study describes a single‐center experience with targeted NGS for patients with sarcoma. Mutations were readily detected and 75 (representing 40% of patients) were testable for therapeutic effect using existing drugs within the confines of a clinical trial. These data indicate that targeted NGS is a useful tool in potentially routing patients to mutation‐specific clinical trials. Further study will be required to determine if these mutations are clinically meaningful drug targets in sarcoma.
Implications for Practice
The sarcomas are a heterogenous family of over 50 different mesenchymal tumors. Current practice for metastatic disease involves systemic chemotherapy or nonspecific kinase inhibitors such as pazopanib. Sarcomas typically lack the classic kinase alterations seen in many carcinomas. The role of next‐generation sequencing in sarcoma clinical practice remains undefined.
This article describes result of targeted next‐generation sequencing in sarcoma patient samples. More than 400 cancerrelated genes were analyzed on a commercia |
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ISSN: | 1083-7159 1549-490X |
DOI: | 10.1634/theoncologist.2017-0290 |