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Genetic profiling as a clinical tool in advanced parathyroid carcinoma

by Sherman, Steven I , Kutahyalioglu, Merve , Ibrahim, Eiman , Silva, Angelica , Williams, Michelle , Perrier, Nancy , Jimenez, Camilo , Dadu, Ramona , Kwatampora, Lily , Clarke, Callisia , Hu, Mimi I , Nguyen, Ha T , Zafereo, Mark , Cabanillas, Maria E , Broaddus, Russell , Busaidy, Naifa L , Waguespack, Steven G , Kopetz, Scott , Wanland, Kacey

in Carcinoma / Esophagus / Genes / Invasiveness / Malignancy / Metastases / Metastasis / Mutation / Neuroendocrine tumors / Next-generation sequencing / p53 Protein / Parathyroid / Tuberous Sclerosis Complex 1 / Tumors

2019

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Genetic profiling as a clinical tool in advanced parathyroid carcinoma

2019

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2019

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Journal Article

Genetic profiling as a clinical tool in advanced parathyroid carcinoma

Sherman, Steven I,

Kutahyalioglu, Merve,

Ibrahim, Eiman,

Silva, Angelica,

Williams, Michelle,

Perrier, Nancy,

Jimenez, Camilo,

Dadu, Ramona,

Kwatampora, Lily,

Clarke, Callisia,

Hu, Mimi I,

Nguyen, Ha T,

Zafereo, Mark,

Cabanillas, Maria E,

Broaddus, Russell,

Busaidy, Naifa L,

Waguespack, Steven G,

Kopetz, Scott,

Wanland, Kacey

2019

Overview

ContextParathyroid carcinoma (PC) is a rare endocrine malignancy with no approved systemic therapies for unresectable locally invasive or distant metastatic disease. Understanding the molecular changes in advanced PC can provide better understanding of this disease and potentially help directing targeted therapy.ObjectiveTo evaluate tumor-specific genetic changes using next-generation sequencing (NGS) panels.DesignAll patients with advanced PC were tested for hot-spot panels using NGS panels including a 50-gene panel, a 409-gene panel if the standard 50-gene panel (Ion Torrent, Life Technology) was negative or a FoundationOne panel.SettingThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.Patients or other participants11 patients with advanced PC were selected to undergo molecular testing.Main outcome measure(s)Genetic profiles of advanced PC.ResultsAmong the 11 patients, 4 patients had the 50-gene panel only, 6 had 409-gene panel after a negative 50-gene panel and 1 had FoundationOne. One patient who had 50-gene panel only also had his metastatic site (esophagus) of his tumor tested with FoundationOne. The most common mutations identified were in the PI3 K (PIK3CA, TSC1 and ATM) (4/11 patients) and TP53 (3/11) pathways. Genes not previously reported to be mutated in PC included: SDHA, TERT promoter and DICER1. Actionable mutations were found in 54% (6/11) of the patients.ConclusionsMutational profiling using NGS panels in advanced PC has yielded important potentially targetable genetic alterations. Larger studies are needed to identify commonly mutated genes in advanced PC patients. Development of novel therapies targeting these cellular pathways should be considered.

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Publisher

Springer Nature B.V

Subject

/ Genes