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Mutational analyses of WNT7A and HDAC11 as candidate tumour suppressor genes in sporadic malignant pancreatic endocrine tumours
Author(s) -
Lindberg Daniel,
Åkerström Göran,
Westin Gunnar
Publication year - 2007
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2006.02694.x
Subject(s) - biology , exon , dna methylation , loss of heterozygosity , gene , tumor suppressor gene , genetics , cancer research , microbiology and biotechnology , carcinogenesis , gene expression , allele
Summary Objective We and others have reported loss of heterozygosity (LOH) on chromosome 3p25 in sporadic malignant pancreatic endocrine tumours (PETs). A common region of deletion on chromosome 3p25 contains numerous genes, including VHL and PPAR γ, that have been excluded previously as candidate tumour suppressor genes by DNA sequencing analysis. We have analysed whether WNT7A or HDAC11 was biallelically inactivated in a group of well‐characterized PETs. Patients and design Ten PETs from eight patients were selected from a previous study, where LOH on chromosome 3p25 was found in 11 out of 22 sporadic PETs. These tumours were examined for inactivating mutations of WNT7A and HDAC11 by direct sequencing of all exons and intron–exon boundaries. Inactivation of WNT7A expression by aberrant CpG island methylation and WNT7A protein expression were evaluated by methylation‐specific polymerase chain reaction (PCR) and immunohistochemistry, respectively. HDAC11 protein expression was also examined. Results No point mutations, deletion or insertions were detected in either WNT7A or HDAC11 in any of the PETs. Two polymorphisms were identified in the third exon of the WNT7A gene. CpG methylation of the WNT7A gene was not detected and the WNT7A and HDAC11 proteins were normally expressed. Conclusion The absence of tumour‐specific somatic events in WNT7A and HDAC11 suggests that these genes are unlikely to have a classical tumour suppressor gene role in sporadic malignant PETs. The putative 3p25 tumour suppressor remains to be identified.