PMID- 24590585
OWN - NLM
STAT- MEDLINE
DCOM- 20140623
LR  - 20220309
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 464
IP  - 5
DP  - 2014 May
TI  - APC alterations are frequently involved in the pathogenesis of acinar cell 
      carcinoma of the pancreas, mainly through gene loss and promoter 
      hypermethylation.
PG  - 553-64
LID - 10.1007/s00428-014-1562-1 [doi]
AB  - 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/beta-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.
FAU - Furlan, Daniela
AU  - Furlan D
AD  - Department of Surgical and Morphological Sciences, University of Insubria, 
      Varese, Italy.
FAU - Sahnane, Nora
AU  - Sahnane N
FAU - Bernasconi, Barbara
AU  - Bernasconi B
FAU - Frattini, Milo
AU  - Frattini M
FAU - Tibiletti, Maria Grazia
AU  - Tibiletti MG
FAU - Molinari, Francesca
AU  - Molinari F
FAU - Marando, Alessandro
AU  - Marando A
FAU - Zhang, Lizhi
AU  - Zhang L
FAU - Vanoli, Alessandro
AU  - Vanoli A
FAU - Casnedi, Selenia
AU  - Casnedi S
FAU - Adsay, Volkan
AU  - Adsay V
FAU - Notohara, Kenji
AU  - Notohara K
FAU - Albarello, Luca
AU  - Albarello L
FAU - Asioli, Sofia
AU  - Asioli S
FAU - Sessa, Fausto
AU  - Sessa F
FAU - Capella, Carlo
AU  - Capella C
FAU - La Rosa, Stefano
AU  - La Rosa S
LA  - eng
PT  - Journal Article
DEP - 20140304
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
SB  - IM
MH  - Carcinoma, Acinar Cell/*genetics
MH  - *DNA Methylation
MH  - DNA Mutational Analysis
MH  - Gene Dosage
MH  - *Genes, APC
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Multiplex Polymerase Chain Reaction
MH  - Pancreatic Neoplasms/*genetics
MH  - *Promoter Regions, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2014/03/05 06:00
MHDA- 2014/06/24 06:00
CRDT- 2014/03/05 06:00
PHST- 2013/10/19 00:00 [received]
PHST- 2014/02/16 00:00 [accepted]
PHST- 2014/01/24 00:00 [revised]
PHST- 2014/03/05 06:00 [entrez]
PHST- 2014/03/05 06:00 [pubmed]
PHST- 2014/06/24 06:00 [medline]
AID - 10.1007/s00428-014-1562-1 [doi]
PST - ppublish
SO  - Virchows Arch. 2014 May;464(5):553-64. doi: 10.1007/s00428-014-1562-1. Epub 2014 
      Mar 4.