Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas

Area of Science:

• Endocrinology
• Oncology
• Genomics

Background:

• Parathyroid carcinoma (PC) is a rare endocrine malignancy with limited treatment options for recurrent or metastatic disease.
• Surgical resection is curative for localized PC, but effective therapies for advanced stages are lacking.
• Identifying molecular targets is crucial for developing novel therapeutic strategies for refractory PC.

Purpose of the Study:

• To investigate the potential of targeted therapies for recurrent or metastatic parathyroid carcinoma.
• To identify actionable genomic alterations in PC using next-generation sequencing (NGS).
• To contribute to the molecular understanding and treatment selection for this rare cancer.

Main Methods:

• DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissues of 19 recurrent or metastatic PC samples.
• A 560-gene panel was sequenced using NGS to identify genomic alterations.
• Genomic data were analyzed to detect actionable mutations and recurrent alterations.

Main Results:

• 190 genomic alterations were identified across 19 PC samples.
• Potentially actionable genomic alterations were found in 47% (9/19) of patients, including mutations in ROS1, PTEN, and TSC1.
• CDC73 mutations were present in 47% (9/19) of samples, with additional recurrent alterations in MSH2 and AR.

Conclusions:

• This study is the first to report a high frequency of actionable genomic alterations in a Chinese PC population.
• The identified alterations provide a basis for selecting novel targeted therapies for PC.
• Findings enhance the molecular understanding of parathyroid carcinoma, paving the way for improved treatment strategies.