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Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 8, pp 1977–1986 | Cite as

Genetic profiling as a clinical tool in advanced parathyroid carcinoma

  • Merve Kutahyalioglu
  • Ha T. Nguyen
  • Lily Kwatampora
  • Callisia Clarke
  • Angelica Silva
  • Eiman Ibrahim
  • Steven G. Waguespack
  • Maria E. Cabanillas
  • Camilo Jimenez
  • Mimi I. Hu
  • Steven I. Sherman
  • Scott Kopetz
  • Russell Broaddus
  • Ramona Dadu
  • Kacey Wanland
  • Michelle Williams
  • Mark Zafereo
  • Nancy Perrier
  • Naifa L. BusaidyEmail author
Original Article – Cancer Research

Abstract

Context

Parathyroid 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.

Objective

To evaluate tumor-specific genetic changes using next-generation sequencing (NGS) panels.

Design

All 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.

Setting

The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Patients or other participants

11 patients with advanced PC were selected to undergo molecular testing.

Main outcome measure(s)

Genetic profiles of advanced PC.

Results

Among 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.

Conclusions

Mutational 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.

Keywords

Parathyroid carcinoma Genetic profiling Next-generation sequencing Targeted therapy 

Notes

Acknowledgements

We wish to thank Mrs. Jennifer Jordan and Mr. Len Jordan for their generous contributions that made this study possible. We thank Bryan Tutt from the Scientific Publications Department at MD Anderson Cancer Center for editing our manuscript.

Funding

Supported by the NIH/NCI under award number P30CA016672 and philanthropic donation from patients

Compliance with ethical standards

Conflict of interest

NLB has received grant funding from Novartis and Bayer and consulting fees from Eisai. MEC has received grant funding from Eisai. MK, HTN, LK, CC, AS, EI, SGW, CJ, MH, SS, SK, RB, RD, KW, MW, MZ, NP: nothing to disclose

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Merve Kutahyalioglu
    • 1
  • Ha T. Nguyen
    • 1
  • Lily Kwatampora
    • 1
  • Callisia Clarke
    • 2
  • Angelica Silva
    • 2
  • Eiman Ibrahim
    • 1
  • Steven G. Waguespack
    • 1
  • Maria E. Cabanillas
    • 1
  • Camilo Jimenez
    • 1
  • Mimi I. Hu
    • 1
  • Steven I. Sherman
    • 1
  • Scott Kopetz
    • 3
  • Russell Broaddus
    • 4
  • Ramona Dadu
    • 1
  • Kacey Wanland
    • 1
  • Michelle Williams
    • 4
  • Mark Zafereo
    • 5
  • Nancy Perrier
    • 2
  • Naifa L. Busaidy
    • 1
    Email author
  1. 1.Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Surgical Oncology, Division of SurgeryThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Gastrointestinal Medical Oncology, Division of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Pathology, Division of Pathology and Laboratory MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Head and Neck Surgery, Division of SurgeryThe University of Texas MD Anderson Cancer CenterHoustonUSA

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