Exome sequencing reveals the genetic landscape and frequent inactivation of PCDHB3 in Chinese rectal cancers

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	Exome sequencing reveals the genetic landscape and frequent inactivation of PCDHB3 in Chinese rectal cancers
	Ye, W; Ling, SP; Liu, RY; Pan, ZZ; Wang, GY; Gao, SJ; Wu, JX; Cao, LH; Dong, LL; Li, YC; Zhou, Y; Du, WY; Meng, XQ; Chen, JN; Guan, XY; He, YL; Pan, CC; Zheng, XFS; Lu, XM; Chen, S; Huang, WL
	2018
发表期刊	JOURNAL OF PATHOLOGY
ISSN	0022-3417
卷号	245 期号:2 页码:222-234
摘要	Colorectal cancer (CRC) is the third most common cancer worldwide, with more than 1.3 million new cases and 690 000 deaths each year. In China, the incidence of CRC has increased dramatically due to dietary and lifestyle changes, to become the fifth leading cause of cancer-related death. Here, we performed whole-exome sequencing in 50 rectal cancer cases among the Chinese population as part of the International Cancer Genome Consortium research project. Frequently mutated genes and enriched pathways were identified. Moreover, a previously unreported gene, PCDHB3, was found frequently mutated in 5.19% cases. Additionally, PCDHB3 expression was found decreased in 81.6% of CRC tissues and all eight CRC cell lines tested. Low expression and cytoplasmic localization of PCDHB3 predict poor prognosis in advanced CRC. Copy number decrease and/or CpG island hypermethylation contributes to the pervasive decreased expression of PCDHB3. PCDHB3 inhibits CRC cell proliferation, migration, and epithelial-mesenchymal transition. The tumor-suppressive effects of PCDHB3 are partially due to inhibition of NF-kappa B transcriptional activity through K63 deubiquitination of p50 at lysine 244/252, which increases the binding affinity of inactive p50 homodimer to kappa B DNA, resulting in competitive inhibition of the transcription of NF-kappa B target genes by p65 dimers. Our study identified PCDHB3 as a novel tumor suppressor in CRC via inhibition of the NF-kappa B pathway, and its expression and localization may serve as prognostic markers for advanced CRC. Copyright (C) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13650
专题	个人在本单位外知识产出
推荐引用方式 GB/T 7714	Ye, W,Ling, SP,Liu, RY,et al. Exome sequencing reveals the genetic landscape and frequent inactivation of PCDHB3 in Chinese rectal cancers[J]. JOURNAL OF PATHOLOGY,2018,245(2):222-234.
APA	Ye, W.,Ling, SP.,Liu, RY.,Pan, ZZ.,Wang, GY.,...&Huang, WL.(2018).Exome sequencing reveals the genetic landscape and frequent inactivation of PCDHB3 in Chinese rectal cancers.JOURNAL OF PATHOLOGY,245(2),222-234.
MLA	Ye, W,et al."Exome sequencing reveals the genetic landscape and frequent inactivation of PCDHB3 in Chinese rectal cancers".JOURNAL OF PATHOLOGY 245.2(2018):222-234.

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2023041201.pdf（4107KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文