Publications

Authors:

Faber, Erik B; Krause, Harris B; Amin, Khalid; Walker, Philip; Hosein, Peter J; Shields, Anthony F; Lenz, Heinz-Josef; Prakash, Ajay; Goel, Sanjay; Oberley, Matthew; Malleo, Giuseppe; Luchini, Claudio; Hwang, Justin; Florou, Vaia; Garrido-Laguna, Ignacio; Lou, Emil

Title:

Genomic Profiling of Rare Undifferentiated Sarcomatoid Subtypes of Pancreatic Carcinomas: In Search of Therapeutic Targets

Year:

2024

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

No

Name of journal:

JCO PRECISION ONCOLOGY

ISSN of journal:

2473-4284

N° Volume:

8

Page numbers:

1-9

Keyword:

undifferentiated sarcomatoid carcinoma (USC), pancreatic ductal adenocarcinoma (PDAC)

Short description of contents:

Purpose: The highly aggressive undifferentiated sarcomatoid carcinoma (USC) subtype of pancreatic ductal adenocarcinoma (PDAC) remains poorly characterized because of its rarity. Previous case reports suggest that immune checkpoint inhibitors could be a promising treatment strategy, but the prevalence of established predictive biomarkers of response is largely unknown. The objective of this study was to leverage comprehensive genomic profiling of USC PDAC tumors to determine the prevalence of biomarkers associated with potential response to targeted therapies. Methods: USC tumors (n = 20) underwent central pathology review by a board-certified gastrointestinal pathologist to confirm the diagnosis. These samples were compared with non-USC PDAC tumors (N = 5,562). Retrospective analysis of DNA and RNA next-generation sequencing data was performed. Results: USC PDACs were more frequently PD-L1+ by immunohistochemistry than non-USC PDAC (63% v 16%, respectively, P < .001). Furthermore, USC PDAC had an increase in neutrophils (8.99% v 5.55%, P = .005) and dendritic cells (1.08% v 0.00%, q = 0.022) and an increased expression of PDCD1LG2 (4.6% v 1.3%, q = 0.001), PDCD1 (2.0% v 0.8%, q = 0.060), and HAVCR2 (45.9% v 21.7%, q = 0.107) than non-USC PDAC. Similar to non-USC PDAC, KRAS was the most commonly mutated gene (86% v 90%, respectively, P = 1). Conclusion: To our knowledge, this work represents the largest molecular analysis of USC tumors to date and showed an increased expression of immune checkpoint genes in USC tumors. These findings provide evidence for further investigation into immune checkpoint inhibitors in USC tumors.

Product ID:

139632

Handle IRIS:

11562/1126387

Last Modified:

August 22, 2024

Bibliographic citation:

Faber, Erik B; Krause, Harris B; Amin, Khalid; Walker, Philip; Hosein, Peter J; Shields, Anthony F; Lenz, Heinz-Josef; Prakash, Ajay; Goel, Sanjay; Oberley, Matthew; Malleo, Giuseppe; Luchini, Claudio; Hwang, Justin; Florou, Vaia; Garrido-Laguna, Ignacio; Lou, Emil, Genomic Profiling of Rare Undifferentiated Sarcomatoid Subtypes of Pancreatic Carcinomas: In Search of Therapeutic Targets «JCO PRECISION ONCOLOGY» , vol. 8 , 2024 , pp. 1-9

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