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Hypermethylation of the APC promoter but lack of APC mutations in myxoid/round‐cell liposarcoma
Author(s) -
Sievers Sonja,
Fritzsch Carla,
Lehnhardt Marcus,
Zahn Susanne,
Kutzner Nadine,
Kuhnen Cornelius,
Müller Oliver
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22117
Subject(s) - adenomatous polyposis coli , biology , dna methylation , myxoid liposarcoma , epigenetics , cancer research , methylation , wnt signaling pathway , loss of heterozygosity , microbiology and biotechnology , liposarcoma , gene , genetics , sarcoma , gene expression , pathology , allele , cancer , medicine , colorectal cancer
The adenomatous polyposis coli (APC) protein is a key component of the WNT signalling pathway wherein it acts as a scaffolding protein in controlling the level of the proto‐oncoprotein β‐catenin. Although APC has been shown to be genetically or epigenetically inactivated in a variety of carcinomas, little is known about its role in sarcoma. Liposarcomas (LPSs) are the second most common soft tissue sarcoma in adults. Despite different histology and malignancy, the myxoid and round‐cell LPSs belong to one tumour entity characterized by a specific chromosomal translocation. We assessed the extent of genetic and epigenetic inactivation of the APC gene in myxoid/round‐cell LPS. Sequencing of the mutation cluster region, the protein truncation test and a loss of heterozygosity (LOH) analysis did not reveal any genetic alterations of the APC gene in all of the liposarcoma samples. Methylation of the APC promoter was detected by methylation‐specific PCR in 9 of 20 (45%) tumours. Analysis of APC expression by semiquantitative RT‐PCR in a subset of the samples demonstrated that tumours with a methylated APC promoter showed a downregulation of the APC transcript. However, APC downregulation was not correlated with a stabilisation of the β‐catenin protein. Thus, the epigenetic regulation of the APC gene might play an important role in the pathogenesis of myxoid/round‐cell LPS. However, the impact of APC methylation on liposarcoma development is quite likely not mediated through WNT signalling. © 2006 Wiley‐Liss, Inc.