In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3138-3138
Abstract:
Purpose: Src cascade is crucial in tumor growth and metastasis development. Nowadays, one of the most relevant mechanisms for gene control is epigenetic mechanisms, both methylation and acetylation. We study the epigenetic regulation of Src pathway in pancreatic adenocarcinomas. The main purpose of this study was to obtain translational results, we can apply in the clinical practice. Methods: 70 pancreatic adenocarcinomas and normal tissue from the same patient were analyzed. DNA from laser microdissected paraffin embedded sample was obtained, bisulfite treated, methylation specific PCR (MSP) amplified, and agarose visualized. Some cases were bisulfite sequenced for verification. Rassf1a, Cox2, Socs, E-Cadherin, DAP-kinase, TIMP3, TWIST1, p16 and Cyclin-D2 genes were analyzed due to their implication with Src pathway. All patients signed informed consent and detail clinic histories were reviewed. Results: We found gene hypermethylation in all the selected targets ranged between 23.5% (DAP-K) to 73% (TWIST1), i.e. RASSF1α (48.7%); p16 (38.2%)… Bisulfite promoter sequence confirms MSP results. Patient clinical profile clustered in some well defined groups. Epigenetic profile also showed very nice association. Combine clinical and epigenetic profile showed a specific and characteristic correlation between some clinical parameters and specific gene methylation profile. In this sense, for instance, we found a perfect match between just RASSF1α promoter hypermethylation with clinical parameters: pTNM and tumor localization. Conclusions: Gene hypermethylation control seems important in pancreatic adenocarcinoma behavior. Src pathway could be implicated in tumoral development, both directly and indirectly (through i.e. EGFR, HER2/Neu, Integrins and SPARC). Src pathway methylation control could be important in development and progression of pancreatic carcinoma (up to 73%). An “epigenetic fingerprint” of pancreatic adenocarcinoma was found from clinical and epigenetic clustering analysis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3138. doi:1538-7445.AM2012-3138
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-3138
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
Permalink