Analysis of CHK2 in vulval neoplasia.
Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia. We identified the previously described silent polymorphism at codon 84 (A>G at nucleotide 252) in the germ-line of six out of 72, and somatic mutations in two out of 40 cases of vulval squamous cell carcinomas and none of 32 cases of vulval intraepithelial neoplasia. One mutation introduced a premature stop codon in the kinase domain of CHK2, whereas the second resulted in an amino acid substitution in the kinase domain. The two squamous cell carcinomas with mutations in CHK2 also expressed mutant p53. A CpG island was identified close to the putative CHK2 transcriptional start site, but methylation-specific PCR did not detect methylation in any of 40 vulval squamous cell carcinomas, irrespective of human papillomavirus or p53 status. Consistent with this observation, no cancer exhibited loss of CHK2 expression at mRNA or protein level. Taken together, these observations reveal that genetic but not epigenetic changes in CHK2 occur in a small proportion of vulval squamous cell carcinomas.
Reddy
A
A
Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Yuille
M
M
Sullivan
A
A
Repellin
C
C
Bell
A
A
Tidy
J A
JA
Evans
D J
DJ
Farrell
P J
PJ
Gusterson
B
B
Gasco
M
M
Crook
T
T
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D064447:Checkpoint Kinase 2; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D014412:Tumor Virus Infections / Q000150:complications / Q000235:genetics; D014846:Vulvar Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases