Genetic Polymorphisms and DNA Methylation Evaluation in a Rare Pediatric Case Carrying a Solid Pseudo Papillary Neoplasm of the Pancreas

Bruna dos Santos Paiva Ribeiro, Vera Lucia Antunes Chagas, Marcelo Soares da Mota e Silva, Gilda Alves, Mariana Chantre-Justino and Maria da Gloria da Costa Carvalho

Background and Objectives: Heterogeneity within the tumour has been described for several types of cancer, including Solid Pseudo Papillary Neoplasm of the Pancreas (SPNP). Tumour heterogeneity may provide distinct molecular signatures that can significantly affect treatment response. This study aimed to investigate the molecular heterogeneity of three different tumour areas (peripheral, intermediate and central) from a pediatric case with SPNP submitted to Whipple’s surgery in the Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil. Materials and Methods: Polymorphisms of the detoxification genes GSTP1, CYPA1m1 and CYPA1m2 were investigated by PCR-restriction fragment length polymorphism (PCR-RFLP) technique and the promoter Methylation profile of the genes p14^ARF, GSTP1, hTERT and MGMT were assessed by Methylation-Specific PCR (MSP). Results: The CYPA1m1 and CYPA1m2 showed wild-type genotype and GSTP1 showed heterozygote genotype. Regarding the methylation status, MGMT showed no detectable methylation in any of the 3 tumour regions; in contrast, both p14^ARF and hTERT showed detectable methylation in all three regions, whereas, GSTP1 showed methylation in peripheral and intermediate areas. Conclusion: Epigenetic inactivation of critical genes and reduced detoxification activity revealed the SPNP tumour biology heterogeneity, which could represent new molecular targets for SPNP treatment.

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