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Background  The Ras Association Domain Family Member 1 ( RASSF1 ) is one of the most frequently reported methylation-inactivated tumor suppressor genes in primary pancreatic ductal adenocarcinomas (PDAC). Limited information is still available about the impact of  RASSF1  gene silencing on the expression of its different isoforms in neoplastic cells.    Methods  A series of 96 primary PDAC, with known clinico-pathological parameters, was tested for  RASSF1  methylation status by methylation-specific PCR,  RASSF1  locus copy number alterations by fluorescence in situ hybridization, and Rassf1a protein expression by immunohistochemistry. A further series of 14 xenografted primary PDAC and 8 PDAC-derived cell lines were tested to obtain a detailed methylation mapping of CpG islands A and C of the  RASSF1  locus by pyrosequencing and to evaluate the expression of Rassf1 variants by qRT-PCR.    Results  Methylation of CpG island A of the  RASSF1  gene was observed in 35 % of the tumors and allelic loss of  RASSF1  locus was seen in 30 disomic and in 20 polysomic cases (52 %). Rassf1a immunohistochemical expression was downregulated in half of primary PDAC, and this downregulation was neither correlated with methylation of  RASSF1  promoter nor with  RASSF1  copy number alterations.  RASSF1  status did not influence patients’ prognosis. The expression of the seven RASSF1 isoforms in xenografts and cell lines showed that RASSF1A, RASSF1B, and RASSF1C isoforms were present in all xenografts and cell lines, whereas RASSF1D, RASSF1E, and RASSF1F isoforms were variably expressed among samples. RASSF1G was never expressed in either xenografts or cell lines. The variable expression of RASSF1 isoforms in PDAC xenografts and cell lines was not dependent on  RASSF1  methylation status of CpG islands A and C.    Conclusions   RASSF1  alterations occurring in PDAC mainly consist in variations of expression of the different isoforms. Different genetic mechanisms seem to contribute to  RASSF1  deregulation in this setting, but  RASSF1  methylation does not seem to substantially affect RASSF1 isoforms expression.    Electronic supplementary material  The online version of this article (doi:10.1186/s12885-016-2048-0) contains supplementary material, which is available to authorized users.

RASSF1 tumor suppressor gene in pancreatic ductal adenocarcinoma: correlation of expression, chromosomal status and epigenetic changes