TY - JOUR
T1 - Genetic profiling as a clinical tool in advanced parathyroid carcinoma
AU - Kutahyalioglu, Merve
AU - Nguyen, Ha T.
AU - Kwatampora, Lily
AU - Clarke, Callisia
AU - Silva, Angelica
AU - Ibrahim, Eiman
AU - Waguespack, Steven G.
AU - Cabanillas, Maria E.
AU - Jimenez, Camilo
AU - Hu, Mimi I.
AU - Sherman, Steven I.
AU - Kopetz, Scott
AU - Broaddus, Russell
AU - Dadu, Ramona
AU - Wanland, Kacey
AU - Williams, Michelle
AU - Zafereo, Mark
AU - Perrier, Nancy
AU - Busaidy, Naifa L.
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - Genetic profiling
KW - Next-generation sequencing
KW - Parathyroid carcinoma
KW - Targeted therapy
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U2 - 10.1007/s00432-019-02945-9
DO - 10.1007/s00432-019-02945-9
M3 - Article
C2 - 31309300
AN - SCOPUS:85068957150
SN - 0171-5216
VL - 145
SP - 1977
EP - 1986
JO - Journal of cancer research and clinical oncology
JF - Journal of cancer research and clinical oncology
IS - 8
ER -