APC alterations are frequently involved in the pathogenesis of acinar cell carcinoma of the pancreas, mainly through gene loss and promoter hypermethylation.

Details

Serval ID
serval:BIB_A2B562B19A10
Type
Article: article from journal or magazin.
Collection
Publications
Title
APC alterations are frequently involved in the pathogenesis of acinar cell carcinoma of the pancreas, mainly through gene loss and promoter hypermethylation.
Journal
Virchows Archiv : An International Journal of Pathology
Author(s)
Furlan D., Sahnane N., Bernasconi B., Frattini M., Tibiletti M.G., Molinari F., Marando A., Zhang L., Vanoli A., Casnedi S., Adsay V., Notohara K., Albarello L., Asioli S., Sessa F., Capella C., La Rosa S.
ISSN
1432-2307 (Electronic)
ISSN-L
0945-6317
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
464
Number
5
Pages
553-564
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Genetic and epigenetic alterations involved in the pathogenesis of pancreatic acinar cell carcinomas (ACCs) are poorly characterized, including the frequency and role of gene-specific hypermethylation, chromosome aberrations, and copy number alterations (CNAs). A subset of ACCs is known to show alterations in the APC/β-catenin pathway which includes mutations of APC gene. However, it is not known whether, in addition to mutation, loss of APC gene function can occur through alternative genetic and epigenetic mechanisms such as gene loss or promoter methylation. We investigated the global methylation profile of 34 tumor suppressor genes, CNAs of 52 chromosomal regions, and APC gene alterations (mutation, methylation, and loss) together with APC mRNA level in 45 ACCs and related peritumoral pancreatic tissues using methylation-specific multiplex ligation probe amplification (MS-MLPA), fluorescence in situ hybridization (FISH), mutation analysis, and reverse transcription-droplet digital PCR. ACCs did not show an extensive global gene hypermethylation profile. RASSF1 and APC were the only two genes frequently methylated. APC mutations were found in only 7 % of cases, while APC loss and methylation were more frequently observed (48 and 56 % of ACCs, respectively). APC mRNA low levels were found in 58 % of cases and correlated with CNAs. In conclusion, ACCs do not show extensive global gene hypermethylation. APC alterations are frequently involved in the pathogenesis of ACCs mainly through gene loss and promoter hypermethylation, along with reduction of APC mRNA levels.
Keywords
Carcinoma, Acinar Cell/genetics, DNA Methylation, DNA Mutational Analysis, Gene Dosage, Genes, APC, Genes, Tumor Suppressor, Humans, In Situ Hybridization, Fluorescence, Multiplex Polymerase Chain Reaction, Pancreatic Neoplasms/genetics, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Create date
06/09/2016 13:49
Last modification date
20/08/2019 16:08
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