Despite the genomic characterization of pancreatic cancer (PC), marked advances in the development of prognosis classification and novel therapeutic strategies have yet to come. The present study aimed to better understand the genomic alterations associated with the invasive phenotype of PC, in order to improve patient selection for treatment options. A total of 30 PC samples were analysed by either whole transcriptome (9 samples) or exome sequencing (21 samples) on an Illumina platform (75X2 or 100X2 bp), and the results were matched with normal DNA to identify somatic events. Single nucleotide variants and insertions and deletions were annotated using public databases, and the pathogenicity of the identified variants was defined according to prior knowledge and mutation-prediction tools. A total of 43 recurrently altered genes were identified, which were involved in numerous pathways, including chromatin remodelling and DNA damage repair. In addition, an analysis limited to a subgroup of early stage patients (50% of samples) demonstrated that poor prognosis was significantly associated with a higher number of known PC mutations (P=0.047). Samples from patients with a better overall survival (>25 months) harboured an average of 24 events, whereas samples from patients with an overall survival of <25 months presented an average of 40 mutations. These findings indicated that a complex genetic profile in the early stage of disease may be associated with increased aggressiveness, thus suggesting an urgent requirement for an innovative approach to classify this disease.

Mutational burden of resectable pancreatic cancer by whole-transcriptome and whole-exome sequencing could predict a poor prognosis

Grassi, Elisa;Durante, Sandra;Astolfi, Annalisa;Tarantino, Giuseppe;Indio, Valentina;Freier, Eva;Casadei, Riccardo;Ricci, Claudio;Comito, Francesca;Filippini, Daria;Formica, Francesca;Serra, Carla;D'Errico, Antonietta;Minni, Francesco;Biasco, Guido;Di Marco, Mariacristina
2018

Abstract

Despite the genomic characterization of pancreatic cancer (PC), marked advances in the development of prognosis classification and novel therapeutic strategies have yet to come. The present study aimed to better understand the genomic alterations associated with the invasive phenotype of PC, in order to improve patient selection for treatment options. A total of 30 PC samples were analysed by either whole transcriptome (9 samples) or exome sequencing (21 samples) on an Illumina platform (75X2 or 100X2 bp), and the results were matched with normal DNA to identify somatic events. Single nucleotide variants and insertions and deletions were annotated using public databases, and the pathogenicity of the identified variants was defined according to prior knowledge and mutation-prediction tools. A total of 43 recurrently altered genes were identified, which were involved in numerous pathways, including chromatin remodelling and DNA damage repair. In addition, an analysis limited to a subgroup of early stage patients (50% of samples) demonstrated that poor prognosis was significantly associated with a higher number of known PC mutations (P=0.047). Samples from patients with a better overall survival (>25 months) harboured an average of 24 events, whereas samples from patients with an overall survival of <25 months presented an average of 40 mutations. These findings indicated that a complex genetic profile in the early stage of disease may be associated with increased aggressiveness, thus suggesting an urgent requirement for an innovative approach to classify this disease.
Grassi, Elisa; Durante, Sandra; Astolfi, Annalisa; Tarantino, Giuseppe; Indio, Valentina; Freier, Eva; Casadei, Riccardo; Ricci, Claudio; Comito, Francesca; Filippini, Daria; Formica, Francesca; Serra, Carla; Santini, Donatella; D'Errico, Antonietta; Minni, Francesco; Biasco, Guido; Di Marco, Mariacristina
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/680941
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