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

Ming Cui, Ya Hu, Yalan Bi, Weiwei Wang, Mengyi Wang, Xiang Zhang, Ronghua Zhang, Peipei Wang, Zhe Su, Xiang Gao, Jiali Wang, Qing Li, Quan Liao, Yupei Zhao

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Parathyroid carcinoma (PC) is a rare endocrine malignancy. Surgical resection is curative for local lesions, while effective therapies are lacking for recurrent or metastatic PCs. To study whether targeted therapies could be applied in recurrent or metastatic PCs, potential therapeutic targets were identified with next-generation sequencing (NGS). DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 19 recurrent or metastatic PC samples. A panel of 560 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 581×. In total, 190 genomic alterations were identified. Nine PC samples (47%) harbored at least one potentially actionable genomic alteration including in the after genes: ROS1 (5/19; 26%), PTEN (3/19; 16%), TSC1 (2/19; 11%), PIK3CA (1/19; 5%), AKT1 (1/19; 5%), MTOR (1/19; 5%), ERBB2 (1/19; 5%), NTRK1 (1/19; 5%), IDH1 (1/19; 5%) and FGFR3 (1/19; 5%). CDC73 mutations were detected in 9/19 (47%) PC samples. Additional recurrent genomic alterations were identified in MSH2 (15/19; 79%), AR (9/19; 47%), BCR (8/19; 42%), SLC45A3 (6/19; 32%), MAGI1 (5/19; 26%), ZNF521 (4/19; 21%), KMT2C (4/19; 21%) and NOTCH4 (4/19; 21%). Our study identified a relatively high frequency of potentially actionable genomic alterations in PC patients in a Chinese population for the first time. A series of recurrent mutant genes was detected as well. Our study contributes to both the selection of novel targeted therapies for PC and further molecular understanding of this refractory malignancy.

Original languageEnglish (US)
Pages (from-to)525-532
Number of pages8
JournalInternational Journal of Cancer
Volume144
Issue number3
DOIs
StatePublished - Feb 1 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Cui, M., Hu, Y., Bi, Y., Wang, W., Wang, M., Zhang, X., Zhang, R., Wang, P., Su, Z., Gao, X., Wang, J., Li, Q., Liao, Q., & Zhao, Y. (2019). Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas. International Journal of Cancer, 144(3), 525-532. https://doi.org/10.1002/ijc.31948