RGD Reference Report - Genetic and epigenetic analysis of CHEK2 in sporadic breast, colon, and ovarian cancers. - Rat Genome Database

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Genetic and epigenetic analysis of CHEK2 in sporadic breast, colon, and ovarian cancers.

Authors: Williams, LH  Choong, D  Johnson, SA  Campbell, IG 
Citation: Williams LH, etal., Clin Cancer Res. 2006 Dec 1;12(23):6967-72.
RGD ID: 2289706
Pubmed: PMID:17145815   (View Abstract at PubMed)
DOI: DOI:10.1158/1078-0432.CCR-06-1770   (Journal Full-text)

PURPOSE: Germ-line variants in CHEK2 have been associated with increased breast, thyroid, prostate, kidney, and colorectal cancer risk; however, the prevalence of somatic inactivation of CHEK2 in common cancer types is less clear. The aim of this study was to determine if somatic mutation and/or epigenetic modification play a role in development of sporadic breast, colon, or ovarian cancers. EXPERIMENTAL DESIGN: We undertook combined genetic and epigenetic analysis of CHEK2 in sporadic primary breast, ovarian, and colon tumors [all exhibiting chromosome 22q loss of heterozygosity (LOH)] and cancer cell lines. Expression of Chk2 was assessed by immunohistochemistry in 119 ovarian tumors. RESULTS: Two novel germ-line variants were identified; however, none of the primary tumors harbored somatic mutations. Two CpG clusters previously implicated in CHEK2 silencing were investigated for evidence of hypermethylation. No methylation was detected at the distal CpG island. The proximal CpG cluster was methylated in all tumor and normal DNA, suggesting that this might not represent a true CpG island and is not relevant in the control of CHEK2 expression. Twenty-three percent of ovarian tumors were negative for Chk2 protein by immunohistochemistry, but there was no significant correlation between LOH across the CHEK2 locus and intensity of Chk2 staining (P = 0.12). CONCLUSIONS: LOH across the CHEK2 locus is common in sporadic breast, ovarian, and colorectal cancers, but point mutation or epigenetic inactivation of the retained allele is uncommon. Loss of Chk2 protein in ovarian cancer was not associated with allelic status, suggesting that inactivation does not occur as a consequence of haploinsufficiency.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast cancer susceptibilityIAGP 2289706DNA:loss of heterozygosityRGD 
breast cancer susceptibilityISOCHEK2 (Homo sapiens)2289706; 2289706DNA:loss of heterozygosityRGD 
colorectal cancer susceptibilityIAGP 2289706DNA:loss of heterozygosityRGD 
colorectal cancer susceptibilityISOCHEK2 (Homo sapiens)2289706; 2289706DNA:loss of heterozygosityRGD 
Ovarian Neoplasms susceptibilityIAGP 2289706DNA:loss of heterozygosityRGD 
Ovarian Neoplasms susceptibilityISOCHEK2 (Homo sapiens)2289706; 2289706DNA:loss of heterozygosityRGD 

Objects Annotated

Genes (Rattus norvegicus)
Chek2  (checkpoint kinase 2)

Genes (Mus musculus)
Chek2  (checkpoint kinase 2)

Genes (Homo sapiens)
CHEK2  (checkpoint kinase 2)


Additional Information