Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

Alexander Semaan; Vincent Bernard; Jaewon J. Lee; Justin W. Wong; Jonathan Huang; Daniel B. Swartzlander; Bret M. Stephens; Maria E. Monberg; Brian R. Weston; Manoop S. Bhutani; Kyle Chang; Paul A. Scheet; Anirban Maitra; Yasminka A. Jakubek; Paola A. Guerrero

doi:10.1158/1078-0432.CCR-20-2667

Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

Alexander Semaan, Vincent Bernard, Jaewon J. Lee, Justin W. Wong, Jonathan Huang, Daniel B. Swartzlander, Bret M. Stephens, Maria E. Monberg, Brian R. Weston, Manoop S. Bhutani, Kyle Chang, Paul A. Scheet, Anirban Maitra, Yasminka A. Jakubek, Paola A. Guerrero

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Purpose: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials. Experimental Design: Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC. Results: Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort. Conclusions: Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.

Original language	English
Pages (from-to)	1082-1093
Number of pages	12
Journal	Clinical Cancer Research
Volume	27
Issue number	4
DOIs	https://doi.org/10.1158/1078-0432.CCR-20-2667
State	Published - Feb 15 2021

Bibliographical note

Funding Information:
We thank A.J. Aguirre, B.M. Wolpin, and the Hale Family Research Center at Dana-Farber Cancer Institute for providing an independent dataset used for replication of our results. Most of all we thank the patients and their families. A. Maitra is supported by the MD Anderson Pancreatic Cancer Moon Shot Program, the Khalifa Bin Zayed Al-Nahyan Foundation, and the NIH (U01CA196403, U01CA200468, and P50CA221707). A. Semaan is supported by the German Research Foundation (SE-2616/2–1). V. Bernard is supported by the NIH (U54CA096300, U54CA096297, and T32CA217789). J.J. Lee is supported by the NIH (T32CA009599).

Funding Information:
A. Semaan reports grants from DFG during the conduct of the study. A. Maitra reports other from Cosmos Wisdom Biotech, Thrive Earlier Detection, and JNJ outside the submitted work. Y.A. Jakubek reports other from Invitae outside the submitted work. No disclosures were reported by the other authors.

Publisher Copyright:
© 2020 American Association for Cancer Research.

ASJC Scopus subject areas

Medicine (all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1078-0432.CCR-20-2667

Cite this

Semaan, A., Bernard, V., Lee, J. J., Wong, J. W., Huang, J., Swartzlander, D. B., Stephens, B. M., Monberg, M. E., Weston, B. R., Bhutani, M. S., Chang, K., Scheet, P. A., Maitra, A., Jakubek, Y. A., & Guerrero, P. A. (2021). Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples. Clinical Cancer Research, 27(4), 1082-1093. https://doi.org/10.1158/1078-0432.CCR-20-2667

@article{622e928672234287b7026c91fa2f71de,

title = "Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples",

abstract = "Purpose: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-na{\"i}ve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials. Experimental Design: Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC. Results: Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort. Conclusions: Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.",

author = "Alexander Semaan and Vincent Bernard and Lee, {Jaewon J.} and Wong, {Justin W.} and Jonathan Huang and Swartzlander, {Daniel B.} and Stephens, {Bret M.} and Monberg, {Maria E.} and Weston, {Brian R.} and Bhutani, {Manoop S.} and Kyle Chang and Scheet, {Paul A.} and Anirban Maitra and Jakubek, {Yasminka A.} and Guerrero, {Paola A.}",

note = "Funding Information: We thank A.J. Aguirre, B.M. Wolpin, and the Hale Family Research Center at Dana-Farber Cancer Institute for providing an independent dataset used for replication of our results. Most of all we thank the patients and their families. A. Maitra is supported by the MD Anderson Pancreatic Cancer Moon Shot Program, the Khalifa Bin Zayed Al-Nahyan Foundation, and the NIH (U01CA196403, U01CA200468, and P50CA221707). A. Semaan is supported by the German Research Foundation (SE-2616/2–1). V. Bernard is supported by the NIH (U54CA096300, U54CA096297, and T32CA217789). J.J. Lee is supported by the NIH (T32CA009599). Funding Information: A. Semaan reports grants from DFG during the conduct of the study. A. Maitra reports other from Cosmos Wisdom Biotech, Thrive Earlier Detection, and JNJ outside the submitted work. Y.A. Jakubek reports other from Invitae outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",

year = "2021",

month = feb,

day = "15",

doi = "10.1158/1078-0432.CCR-20-2667",

language = "English",

volume = "27",

pages = "1082--1093",

number = "4",

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Semaan, A, Bernard, V, Lee, JJ, Wong, JW, Huang, J, Swartzlander, DB, Stephens, BM, Monberg, ME, Weston, BR, Bhutani, MS, Chang, K, Scheet, PA, Maitra, A, Jakubek, YA & Guerrero, PA 2021, 'Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples', Clinical Cancer Research, vol. 27, no. 4, pp. 1082-1093. https://doi.org/10.1158/1078-0432.CCR-20-2667

TY - JOUR

T1 - Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

AU - Semaan, Alexander

AU - Bernard, Vincent

AU - Lee, Jaewon J.

AU - Wong, Justin W.

AU - Huang, Jonathan

AU - Swartzlander, Daniel B.

AU - Stephens, Bret M.

AU - Monberg, Maria E.

AU - Weston, Brian R.

AU - Bhutani, Manoop S.

AU - Chang, Kyle

AU - Scheet, Paul A.

AU - Maitra, Anirban

AU - Jakubek, Yasminka A.

AU - Guerrero, Paola A.

N1 - Funding Information: We thank A.J. Aguirre, B.M. Wolpin, and the Hale Family Research Center at Dana-Farber Cancer Institute for providing an independent dataset used for replication of our results. Most of all we thank the patients and their families. A. Maitra is supported by the MD Anderson Pancreatic Cancer Moon Shot Program, the Khalifa Bin Zayed Al-Nahyan Foundation, and the NIH (U01CA196403, U01CA200468, and P50CA221707). A. Semaan is supported by the German Research Foundation (SE-2616/2–1). V. Bernard is supported by the NIH (U54CA096300, U54CA096297, and T32CA217789). J.J. Lee is supported by the NIH (T32CA009599). Funding Information: A. Semaan reports grants from DFG during the conduct of the study. A. Maitra reports other from Cosmos Wisdom Biotech, Thrive Earlier Detection, and JNJ outside the submitted work. Y.A. Jakubek reports other from Invitae outside the submitted work. No disclosures were reported by the other authors. Publisher Copyright: © 2020 American Association for Cancer Research.

PY - 2021/2/15

Y1 - 2021/2/15

N2 - Purpose: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials. Experimental Design: Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC. Results: Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort. Conclusions: Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.

AB - Purpose: Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials. Experimental Design: Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC. Results: Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort. Conclusions: Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.

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UR - http://www.scopus.com/inward/citedby.url?scp=85101765956&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-20-2667

DO - 10.1158/1078-0432.CCR-20-2667

M3 - Article

C2 - 33188144

AN - SCOPUS:85101765956

SN - 1078-0432

VL - 27

SP - 1082

EP - 1093

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 4

ER -

Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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