Molecular Characterization of Pancreatic Ductal Adenocarcinoma Using a Next-Generation Sequencing Custom-Designed Multigene Panel

被引:9
|
作者
Malvi, Deborah [1 ]
Vasuri, Francesco [1 ]
Maloberti, Thais [2 ,3 ]
Sanza, Viviana [3 ]
De Leo, Antonio [2 ,3 ]
Fornelli, Adele [4 ]
Masetti, Michele [5 ]
Benini, Claudia [5 ]
Lombardi, Raffaele [5 ]
Offi, Maria Fortuna [5 ]
Di Marco, Mariacristina [6 ,7 ]
Ravaioli, Matteo [8 ,9 ]
Fiorino, Sirio [10 ]
Franceschi, Enrico [11 ]
Brandes, Alba A. [11 ]
Jovine, Elio [5 ]
D'Errico, Antonietta [1 ]
Tallini, Giovanni [2 ,3 ]
de Biase, Dario [12 ]
机构
[1] Azienda Osped Univ Bologna, IRCCS, Pathol Unit, I-40138 Bologna, Italy
[2] Univ Bologna, Azienda USL Bologna, Mol Diagnost Unit, Dept Expt Diagnost & Specialty Med, I-40138 Bologna, Italy
[3] Azienda Osped Univ Bologna, IRCCS, Div Mol Pathol, I-40138 Bologna, Italy
[4] Maggiore Hosp, Azienda USL, Anat Pathol Unit, I-40133 Bologna, Italy
[5] Azienda Osped Univ Bologna, Maggiore Hosp, IRCCS, Dept Gen Surg, I-40133 Bologna, Italy
[6] Azienda Osped Univ Bologna, IRCCS, Div Med Oncol, I-40138 Bologna, Italy
[7] Univ Bologna, Dept Specialized Expt & Diagnost Med, I-40138 Bologna, Italy
[8] Azienda Osped Univ Bologna, IRCCS, Dept Gen Surg & Transplantat, I-40138 Bologna, Italy
[9] Univ Bologna, Dipartimento Sci Med & Chirurg DIMEC, I-40126 Bologna, Italy
[10] Azienda USL Bologna, Budrio Hosp, Internal Med Unit, I-40054 Bologna, Italy
[11] IRCSS Ist Sci Neurol Bologna, Nervous Syst Med Oncol Dept, I-40139 Bologna, Italy
[12] Univ Bologna, Dept Pharm & Biotechnol FaBiT, I-40138 Bologna, Italy
关键词
pancreatic cancer; PDAC; next-generation sequencing; KRAS; TP53; mutations; LONG-TERM SURVIVORS; INTRAEPITHELIAL NEOPLASIA; GENETIC ALTERATIONS; EARLY RECURRENCE; CANCER; RESECTION; TP53; GEMCITABINE; PROGRESSION; ERLOTINIB;
D O I
10.3390/diagnostics12051058
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence compared with KRAS wild-type tumors. Intriguingly, KRAS wild-type cases had a better short-term prognosis despite the lymph node status. In conclusion, our work highlights that the combination of KRAS mutation with the age of the patient and the lymph node status may help in predicting the outcome in PDAC patients.
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页数:11
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