Should next-generation sequencing tests be performed on all cancer patients?

McKenzie, Andrew J.; Dilks, Holli H.; Jones, Suzanne F.; Burris, Howard A.

doi:10.1080/14737159.2019.1564043

Cited by 28 publications

(26 citation statements)

References 32 publications

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“…Information on whether and when NGS-based genomic testing should be carried out in patients with CCA is currently lacking in the literature. However, this question has been examined more generally in patients with cancer, [63][64][65][66][67] and reference to these findings shed light on when NGS might be useful in patients with CCA. In general, it has been suggested that NGS may not be clinically warranted in patients with early-stage cancer, because molecular profiling in these patients is unlikely to yield actionable genetic alterations other than those that could be identified from conventional approaches (see below).…”

Section: Genomic Profiling To Guide Treatment Decisionsmentioning

confidence: 99%

Practical considerations in screening for genetic alterations in cholangiocarcinoma

2021

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Cholangiocarcinoma (CCA) encompasses diverse epithelial tumors historically associated with poor outcomes due to an aggressive disease course, late diagnosis, and limited benefit of standard chemotherapy for advanced disease. Comprehensive molecular profiling has revealed a diverse landscape of genomic alterations as oncogenic drivers in CCA. TP53 mutations, CDKN2A/B loss, and KRAS mutations are the most common genetic alterations in CCA. However, intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) differ substantially in the frequency of many alterations. This includes actionable alterations, such as isocitrate dehydrogenase 1 (IDH1) mutations and a large variety of FGFR2 rearrangements, which are found in up to 29% and w10% of patients with iCCA, respectively, but are rare in eCCA. FGFR2 rearrangements are currently the only genetic alteration in CCA for which a targeted therapy, the fibroblast growth factor receptor 1-3 inhibitor pemigatinib, has been approved. However, favorable phase III results for IDH1-targeted therapy with ivosidenib in iCCA have been published, and numerous other alterations are actionable by targeted therapies approved in other indications. Recent advances in next-generation sequencing (NGS) have led to the development of assays that allow comprehensive genomic profiling of large gene panels within 2-3 weeks, including in vitro diagnostic tests approved in the United States. These assays vary regarding acceptable source material (tumor tissue or peripheral whole blood), genetic source for library construction (DNA or RNA), target selection technology, gene panel size, and type of detectable genomic alterations. While some large commercial laboratories offer rapid and comprehensive genomic profiling services based on proprietary assay platforms, clinical centers may use commercial genomic profiling kits designed for clinical research to develop their own customized laboratory-developed tests. Large-scale genomic profiling based on NGS allows for a detailed and precise molecular diagnosis of CCA and provides an important opportunity for improved targeted treatment plans tailored to the individual patient's genetic signature.

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Section: Genomic Profiling To Guide Treatment Decisionsmentioning

confidence: 99%

Practical considerations in screening for genetic alterations in cholangiocarcinoma

2021

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“…In contrast, other authors advocate that routine upfront NGS testing should be used for all patients with metastatic cancer with limited standard of care options [41] . In addition, the use of multiplatform technologies seems to identify a higher number of potential targets than conventional consecutive molecular testing and this might subsequently translate in a higher probability to detect an effective matching drug [42] .…”

Section: When Should a Ngs Test Be Considered Clinically In 2020mentioning

confidence: 99%

When should we order a next generation sequencing test in a patient with cancer?

et al. 2020

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Technical advances in genome sequencing and the implementation of next-generation sequencing (NGS) in clinical oncology have paved the way for individualizing cancer patient therapy based on molecular profiles. When and how to use NGS testing in the clinic is at present an unsolved issue, although new research results provide evidence favoring this approach in some types of advanced cancer. Clinical research is evolving rapidly, from basket and umbrella trials to adaptative design precision oncology clinical studies, and genomic and molecular data often displace the classical clinical validation procedures of biomarkers. In this context, physicians must be aware of the clinical evidence behind these new biomarkers and NGS tests available, in order to use them in the right moment, and with a critical point of view. This review will present the status of currently available targeted drugs that can be effective based on actionable molecular alterations, and the NGS tests that are currently available, offering a practical guide for the application of Clinical Precision Oncology in the real world routine practice.

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“…NGS‐based somatic genetic testing, typically used for somatic cancer testing, here ended a diagnostic odyssey and also served to propel management (McKenzie et al, 2019). High depth sequencing has increasingly become a diagnostic method of choice for somatic overgrowth conditions, with a diagnostic yield ranging from 33% to 67% (Chang et al, 2017; Kuentz et al, 2017; Lalonde et al, 2019; Mirzaa et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)

Chenbhanich

Hetts

et al. 2021

American J of Med Genetics Pt A

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Activating variants in the platelet‐derived growth factor receptor β gene (PDGFRB) have been associated with Kosaki overgrowth syndrome, infantile myofibromatosis, and Penttinen premature aging syndrome. A recently described phenotype with fusiform aneurysm has been associated with mosaic PDGFRB c.1685A > G p.(Tyr562Cys) variant. Few reports however have examined the vascular phenotypes and mosaic effects of PDGFRB variants. We describe clinical characteristics of two patients with a recurrent mosaic PDGFRB p.(Tyr562Cys) variant identified via next‐generation sequencing‐based genetic testing. We observed intracranial fusiform aneurysm in one patient and found an additional eight patients with aneurysms and phenotypes associated with PDGFRB‐activating variants through literature search. The conditions caused by PDGFRB‐activating variants share overlapping features including overgrowth, premature aged skin, and vascular malformations including aneurysms. Aneurysms are progressive and can result in morbidities and mortalities in the absence of successful intervention. Germline and/or somatic testing for PDGFRB gene should be obtained when PDGFRB activating variant‐related phenotypes are present. Whole‐body imaging of the arterial tree and echocardiography are recommended after diagnosis. Repeating the imaging study within a 6‐ to 12‐month period after detection is reasonable. Finally, further evaluation for the effectiveness and safety profile of kinase inhibitors in this patient population is warranted.

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Should next-generation sequencing tests be performed on all cancer patients?

Cited by 28 publications

References 32 publications

Practical considerations in screening for genetic alterations in cholangiocarcinoma

Practical considerations in screening for genetic alterations in cholangiocarcinoma

When should we order a next generation sequencing test in a patient with cancer?

Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys)

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