Digging into the NGS Information from a Large-Scale South European Population with Metastatic/Unresectable Pancreatic Ductal Adenocarcinoma: A Real-World Genomic Depiction

• Published in: Cancers Vol. 16; no. 1; p. 2
• Main Authors: Ziogas, Dimitrios C, Papadopoulou, Eirini, Gogas, Helen, Sakellariou, Stratigoula, Felekouras, Evangellos, Theocharopoulos, Charalampos, Stefanou, Dimitra T, Theochari, Maria, Boukovinas, Ioannis, Matthaios, Dimitris, Koumarianou, Anna, Zairi, Eleni, Liontos, Michalis, Koutsoukos, Konstantinos, Metaxa-Mariatou, Vasiliki, Kapetsis, George, Meintani, Angeliki, Tsaousis, Georgios N, Nasioulas, George
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.12.2023; MDPI
• Subjects: Adenocarcinoma; Analysis; Biomarkers; BRCA1 protein; BRCA2 protein; Cancer; ErbB-2 protein; FANCC protein; FDA approval; Gene mutations; Genes; Genetic aspects; Genomics; Immunotherapy; Metastases; Mutation; Next-generation sequencing; p53 Protein; Pancreas; Pancreatic cancer; Patients; PD-L1 protein; Precision medicine; Risk factors; Scientific equipment and supplies industry; Smad4 protein; Tumor proteins; Tumors; Greece; United States; United States > US; HRR; KRAS; genomic mutation; next generation sequencing; pancreatic ductal adenocarcinoma
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16010002

Despite ongoing oncological advances, pancreatic ductal adenocarcinoma (PDAC) continues to have an extremely poor prognosis with limited targeted and immunotherapeutic options. Its genomic background has not been fully characterized yet in large-scale populations all over the world. Methods: Replicating a recent study from China, we collected tissue samples from consecutive Greek patients with pathologically-confirmed metastatic/unresectable PDAC and retrospectively investigated their genomic landscape using next generation sequencing (NGS). Findings: From a cohort of 409 patients, NGS analysis was successfully achieved in 400 cases (56.50% males, median age: 61.8 years). Consistent with a previous study, was the most frequently mutated gene in 81.50% of tested samples, followed by (50.75%), (8%), and (7.50%). variants with on-label indications were detected in 2%, and 87.50% carried a variant associated with off-label treatment ( , , , or HRR-genes), while 3.5% of the alterations had unknown/preliminary-studied actionability ( ). Most of HRR-alterations were in intermediate- and low-risk genes ( , , , , , , , ), with controversial actionability: 8% harbored a somatic non- alteration, 6 cases had a high-risk alteration ( , ), and one co-presented a alteration. Elevated LOH was associated with HRR-mutated status and mutations while lowered LOH was associated with alterations. Including TMB/MSI data, the potential benefit from an NGS-oriented treatment was increased from 1.91% to 13.74% (high-MSI: 0.3%, TMB > 10 muts/MB: 12.78%). TMB was slightly increased in females (4.75 vs. 4.46 muts/MB) and in individuals with age > 60 (4.77 vs. 4.40 muts/MB). About 28.41% showed PD-L1 > 1% either in tumor or immune cells, 15.75% expressed PD-L1 ≥ 10%, and only 1.18% had PD-L1 ≥ 50%. This is the largest depiction of real-world genomic characteristics of European patients with PDAC, which offers some useful clinical and research insights.