Elsevier

Neoplasia

Volume 10, Issue 11, November 2008, Pages 1253-1258, IN27-IN32
Neoplasia

Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer1,2

https://doi.org/10.1593/neo.08718Get rights and content
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open access

Abstract

Chromodomain, helicase, DNA binding 5 (CHD5) is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04). The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.

Abbreviations

CN
copy number
HRM
high-resolution melt
LOH
loss of heterozygosity

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1

This study was funded by the Victorian Breast Cancer Research Consortium, Australia. M.R. is a recipient of a Cancer Council of Australia Postgraduate Scholarship. W.Q. is a recipient of a National Health and Medical Research Council Dora Lush Postgraduate Scholarship. J.L.B. is a recipient of a University of Melbourne Research Scholarship.

2

This article refers to supplementary materials, which are designated by Tables W1 to W3 and Figures W1 to W3 and are available online at www.neoplasia.com.