癌症研究
体细胞
KEAP1型
种系突变
生物
癌症
突变
医学
病理
基因
遗传学
转录因子
作者
Nam Jin Yoo,Hyung-Ran Kim,Yoo Ri Kim,Chang Hyeok An,Sug Hyung Lee
出处
期刊:Histopathology
[Wiley]
日期:2012-02-20
卷期号:60 (6): 943-952
被引量:205
标识
DOI:10.1111/j.1365-2559.2012.04178.x
摘要
Yoo N J, Kim H R, Kim Y R, An C H & Lee S H (2012) Histopathology 60, 943–952 Somatic mutations of the KEAP1 gene in common solid cancers Aims: KEAP1 inhibits nuclear factor erythroid 2‐related factor 2 (NRF2)‐induced cytoprotection, and is considered to be a candidate tumour suppressor. Somatic mutation of NRF2 has been analysed in a wide variety of human cancers, whereas somatic mutation of KEAP1 has been reported only in lung and gall bladder cancers. The aim of our study was to investigate whether KEAP1 mutations are widespread in human cancers. Methods and results: We analysed 499 cancer tissues from lung, breast, colon, stomach, liver, larynx and prostate, and leukaemias, by single‐strand conformation polymorphism analysis. We detected somatic mutations of KEAP1 in gastric (11.1%), hepatocellular (8.9%), colorectal (7.8%), lung (4.6%), breast (2.0%) and prostate (1.3%) carcinomas. Allelic losses of the KEAP1 locus were identified in 42.9% of cancers with KEAP1 mutations, but no NRF2 mutations were detected in these cancers. The NRF2‐activated cytoprotective proteins (NAD(P)H dehydrogenase quinone 1 and glutamine‐cysteine ligase catalytic subunit) were expressed in all of the cancers with KEAP1 mutations. Conclusions: Our data show that KEAP1 mutations occur widely in solid cancers, irrespective of histological type. Biallelic inactivation of KEAP1 and increased levels of cytoprotective proteins in the cancers suggest that KEAP1 mutations might protect cancer cells from oxidative insults and play a role in the development of solid cancers.
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