TY - JOUR
T1 - A pilot study to evaluate tissue- And plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms
AU - Park, Margaret A.
AU - Zaw, Thinzar
AU - Yoder, Sean J.
AU - Gomez, Maria
AU - Genilo-Delgado, Maria
AU - Basinski, Toni
AU - Katende, Esther
AU - Dam, Aamir
AU - Mok, Shaffer R.S.
AU - Monteiro, Alvaro
AU - Mohammadi, Amir
AU - Jeong, Daniel K.
AU - Jiang, Kun
AU - Centeno, Barbara A.
AU - Hodul, Pamela
AU - Malafa, Mokenge
AU - Fleming, Jason
AU - Chen, Dung Tsa
AU - Mo, Qianxing
AU - Teer, Jamie K.
AU - Permuth, Jennifer B.
N1 - Publisher Copyright:
© 2023 Genetics Society of America. All rights reserved.
PY - 2023/2
Y1 - 2023/2
N2 - Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or focus of invasion preoperatively. The objective of this pilot study was to determine the frequency and type of DNA mutations in a cohort of surgically resected, pathologically confirmed IPMN, and to determine if concordant mutations are detectable in paired pretreatment plasma samples. Formalin-fixed paraffin-embedded (FFPE) tissue from 46 surgically resected IPMNs (31 low-grade, 15 high-grade) and paired plasma from a subset of 15 IPMN cases (10 low-grade, 5 high-grade) were subjected to targeted mutation analysis using a QIAseq Targeted DNA Custom Panel. Common driver mutations were detected in FFPE from 44 of 46 (95.6%) IPMN cases spanning all grades; the most common DNA mutations included: KRAS (80%), RNF43 (24%), and GNAS (43%). Of note, we observed a significant increase in the frequency of RNF43 mutations from low-grade to high-grade IPMNs associated or concomitant with invasive carcinoma (trend test, P = 0.01). Among the subset of cases with paired plasma, driver mutations identified in the IPMNs were not detected in circulation. Overall, our results indicate that mutational burden for IPMNs is a common occurrence, even in low-grade IPMNs. Furthermore, although blood-based biopsies are an attractive, noninvasive method for detecting somatic DNA mutations, the QIAseq panel was not sensitive enough to detect driver mutations that existed in IPMN tissue using paired plasma in the volume we were able to retrieve for this retrospective study.
AB - Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or focus of invasion preoperatively. The objective of this pilot study was to determine the frequency and type of DNA mutations in a cohort of surgically resected, pathologically confirmed IPMN, and to determine if concordant mutations are detectable in paired pretreatment plasma samples. Formalin-fixed paraffin-embedded (FFPE) tissue from 46 surgically resected IPMNs (31 low-grade, 15 high-grade) and paired plasma from a subset of 15 IPMN cases (10 low-grade, 5 high-grade) were subjected to targeted mutation analysis using a QIAseq Targeted DNA Custom Panel. Common driver mutations were detected in FFPE from 44 of 46 (95.6%) IPMN cases spanning all grades; the most common DNA mutations included: KRAS (80%), RNF43 (24%), and GNAS (43%). Of note, we observed a significant increase in the frequency of RNF43 mutations from low-grade to high-grade IPMNs associated or concomitant with invasive carcinoma (trend test, P = 0.01). Among the subset of cases with paired plasma, driver mutations identified in the IPMNs were not detected in circulation. Overall, our results indicate that mutational burden for IPMNs is a common occurrence, even in low-grade IPMNs. Furthermore, although blood-based biopsies are an attractive, noninvasive method for detecting somatic DNA mutations, the QIAseq panel was not sensitive enough to detect driver mutations that existed in IPMN tissue using paired plasma in the volume we were able to retrieve for this retrospective study.
KW - biomarkers
KW - circulating DNA
KW - early detection
KW - pancreatic cancer
KW - pancreatic cysts
KW - somatic mutations
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U2 - 10.1093/g3journal/jkac314
DO - 10.1093/g3journal/jkac314
M3 - Article
C2 - 36454217
AN - SCOPUS:85147834413
SN - 2160-1836
VL - 13
JO - G3: Genes, Genomes, Genetics
JF - G3: Genes, Genomes, Genetics
IS - 2
M1 - jkac314
ER -