Background Pancreatic cancer is among the most aggressive cancer types with a median survival of about 3-6 month for inoperable disease (80-85%). The genetic landscape for primary tumors has been described in the last decades. However, little is known on the genome and proteome of metastases which is surprising against the background that the majority of patients are not suitable for surgical therapy. Thus, we investigated 25 primary tumors and their corresponding metastases by massive parallel sequencing (MPS) and imaging mass spectrometry (IMS) in order to reveal their genetic and proteomic properties. Methods A total of 25 formalin fixed and paraffin embedded primary tumors and their corresponding metastases were analyzed. MPS studies have been conducted as previously described with a custom build pancreatic cancer panel that covers all pancreatic mutations detected with a frequency of more than 1% according to the COSMIC database. IMS studies were performed as previously described on an Autoflex II mass spectrometer. Approximately 500 different peptides were detected per sample. Results Both, MPS and IMS studies revealed highly concordant results in primary tumors and their corresponding metastases. In few primary tumors and also in several metastases additional mutations could be demonstrated. As with the mutational status, only few aberrant peptide profiles were detected in the two subgroups. Conclusions Overall the genetic and the proteomic landscape of pancreatic primaries is similar to that of their corresponding metastases.
Genomic and proteomic landscape of pancreatic primary tumors and their metastases
Casadonte R;
2016-01-01
Abstract
Background Pancreatic cancer is among the most aggressive cancer types with a median survival of about 3-6 month for inoperable disease (80-85%). The genetic landscape for primary tumors has been described in the last decades. However, little is known on the genome and proteome of metastases which is surprising against the background that the majority of patients are not suitable for surgical therapy. Thus, we investigated 25 primary tumors and their corresponding metastases by massive parallel sequencing (MPS) and imaging mass spectrometry (IMS) in order to reveal their genetic and proteomic properties. Methods A total of 25 formalin fixed and paraffin embedded primary tumors and their corresponding metastases were analyzed. MPS studies have been conducted as previously described with a custom build pancreatic cancer panel that covers all pancreatic mutations detected with a frequency of more than 1% according to the COSMIC database. IMS studies were performed as previously described on an Autoflex II mass spectrometer. Approximately 500 different peptides were detected per sample. Results Both, MPS and IMS studies revealed highly concordant results in primary tumors and their corresponding metastases. In few primary tumors and also in several metastases additional mutations could be demonstrated. As with the mutational status, only few aberrant peptide profiles were detected in the two subgroups. Conclusions Overall the genetic and the proteomic landscape of pancreatic primaries is similar to that of their corresponding metastases.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.


