Reduced CRYL1 expression in hepatocellular carcinoma confers cell growth advantages and correlates with adverse patient prognosis

The Journal of Pathology
Ibis K C ChengNathalie Wong

Abstract

Homozygous deletion screening has been widely utilized to define tumour suppressor genes (TSGs) in cancers. Although these biallelic deletions are infrequent, their identification has facilitated the discovery of many important TSGs. We have systematically examined the genome of hepatocellular carcinoma (HCC), a highly malignant tumour that is rapidly fatal, for the presence of homozygous deletions. Array-CGH analysis on early passage of HCC cultures and cell lines led us to identify six homozygous deleted (HD) regions. A high concordance between array-CGH and expression of HD genes was demonstrated, where crystallin Lambda1 (CRYL1; located on chromosome 13q12.11) displayed the most frequent down-regulation. We found that reduced mRNA expression of CRYL1 was common in HCC tumours when compared with their adjacent non-tumoural liver (p = 0.0097). Significant associations could also be drawn between repressed CRYL1 and advanced tumour staging, increased tumour size, and shorter disease-free survival of patients (p < 0.037). Moreover, homozygous deletions on CRYL1 could be detected in 36% of HCC cases, where recurrent HDs were identified on exons 1, 5, and 8. Examination of other causal events suggested histone deacetylation and p...Continue Reading

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Citations

May 24, 2014·European Journal of Haematology·Alexandra SchifferliThomas Kühne
Jan 24, 2015·International Journal of Cancer. Journal International Du Cancer·Zhuang-Zhuang ZhangZe-Guang Han
Jun 19, 2012·Annual Review of Genomics and Human Genetics·Ze-Guang Han
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kit-Ying ChungNathalie Wong

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