In:
Current Pharmaceutical Biotechnology, Bentham Science Publishers Ltd., Vol. 21, No. 2 ( 2020-02-12), p. 140-148
Abstract:
Castration-resistant Prostate Cancer (CRPC) is a fatal disease with rapid growth.
The malignancy usually presents with metastasis and poor prognosis, and causes 100% mortality. Therefore, the treatment of CRPC is extremely challenging, and its pathogenesis need to be elucidated urgently. Objective: The high throughput sequencing technology was used to sequence the whole exome associated
with CRPC, to explore the molecular mechanism of CRPC, and to find the potential therapeutic targets. Methods: We performed whole-exome sequencing of FFPE tissue from 11 Chinese adult male patients.
Genomic DNA was fragmented and enriched for whole-exome sequencing using the QiAamp DNA FFPE Tissue KIT, sequenced on an Illumina HiSeq2000 platform, and the relevant genes were
analyzed using biological information. Finally, immunohistochemistry method was used to detect the phosphorylation level of LATS1 in CRPC tissues of MST1 mutant and non-mutant patients. Results: We have screened 85 significant mutant genes with relatively high mutation rates of TP53,
AR, KMT2, DMAPK1, PIK3R1, SH2B3, WHSC1, KMT2D, MST1 and MAPK1. We first found that MST1 has multiple mutations in CRPC patients, and the MST1 plays an important role in the Hippo
pathway. Immunohistochemistry results showed that the phosphorylation level of LATS1 in the mutant patients was significantly lower than that in the non-mutant patients. Conclusion: We speculate that MST1 would be a new potential target for the treatment of CRPC by
regulating Hippo signaling pathway. The results provided an important clue to the molecular mechanism of CRPC.
Type of Medium:
Online Resource
ISSN:
1389-2010
DOI:
10.2174/1389201019666191003142119
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2020
SSG:
15,3
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