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

2 Citations (Scopus)

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

Fingerprint

Parathyroid Neoplasms
Therapeutics
Genes
Paraffin
Formaldehyde
Neoplasms
Mutation
DNA
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Cui, Ming ; Hu, Ya ; Bi, Yalan ; Wang, Weiwei ; Wang, Mengyi ; Zhang, Xiang ; Zhang, Ronghua ; Wang, Peipei ; Su, Zhe ; Gao, Xiang ; Wang, Jiali ; Li, Qing ; Liao, Quan ; Zhao, Yupei. / Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas. In: International Journal of Cancer. 2019 ; Vol. 144, No. 3. pp. 525-532.
@article{44feefe49e1244fd9f5a83354a9efdd9,
title = "Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas",
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.",
author = "Ming Cui and Ya Hu and Yalan Bi and Weiwei Wang and Mengyi Wang and Xiang Zhang and Ronghua Zhang and Peipei Wang and Zhe Su and Xiang Gao and Jiali Wang and Qing Li and Quan Liao and Yupei Zhao",
year = "2019",
month = "2",
day = "1",
doi = "10.1002/ijc.31948",
language = "English (US)",
volume = "144",
pages = "525--532",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

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, vol. 144, no. 3, pp. 525-532. https://doi.org/10.1002/ijc.31948

Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas. / Cui, Ming; Hu, Ya; Bi, Yalan; Wang, Weiwei; Wang, Mengyi; Zhang, Xiang; Zhang, Ronghua; Wang, Peipei; Su, Zhe; Gao, Xiang; Wang, Jiali; Li, Qing; Liao, Quan; Zhao, Yupei.

In: International Journal of Cancer, Vol. 144, No. 3, 01.02.2019, p. 525-532.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preliminary exploration of potential molecular therapeutic targets in recurrent and metastatic parathyroid carcinomas

AU - Cui, Ming

AU - Hu, Ya

AU - Bi, Yalan

AU - Wang, Weiwei

AU - Wang, Mengyi

AU - Zhang, Xiang

AU - Zhang, Ronghua

AU - Wang, Peipei

AU - Su, Zhe

AU - Gao, Xiang

AU - Wang, Jiali

AU - Li, Qing

AU - Liao, Quan

AU - Zhao, Yupei

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058010481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058010481&partnerID=8YFLogxK

U2 - 10.1002/ijc.31948

DO - 10.1002/ijc.31948

M3 - Article

C2 - 30362515

AN - SCOPUS:85058010481

VL - 144

SP - 525

EP - 532

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -