Potential for clinical management of pancreatic cancer through whole exome profiling of site-specific metastases and matched primary tumors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F25%3A10498978" target="_blank" >RIV/00216208:11140/25:10498978 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/25:73634564 RIV/00098892:_____/25:10159331 RIV/00669806:_____/25:10498978 RIV/75010330:_____/25:00015027
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MuFhDzxj2S" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MuFhDzxj2S</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.labinv.2025.104205" target="_blank" >10.1016/j.labinv.2025.104205</a>
Alternative languages
Result language
angličtina
Original language name
Potential for clinical management of pancreatic cancer through whole exome profiling of site-specific metastases and matched primary tumors
Original language description
Considering the lack of molecular background of the metastatic process in pancreatic ductal adenocarcinoma (PDAC) and fact that the location of the metastasis may carry prognostic information and potential therapeutic opportunities, we aimed to explore genomic profiles of metastases from diverse loci and their value for the patients' therapeutic management. DNA samples from paired primary and metastatic tissue of 20 patients were microdissected and sequenced using whole exome target enrichment. Somatic genetic variability, copy number variations (CNVs), and mutational signatures were assessed for associations with clinical data of patients. KRAS (78% in primary tumors-74% in metastases), TP53 (67-68%), CDKN2A (28-37%), and SMAD4 (22-26%) were the most commonly mutated oncodrivers in primary tumors and metastases. Other frequently mutated genes were CCDC187 (50%-58%), MUC5AC (50%-53%), EPPK1 (39%-63%), SYN2 (39%-26%), MUC19 (33%-47%), MUC3A (33%-26%), DNAH12 (28%-37%), ZBED3 (22%-26%), PKHD1L1 (28%-16%), and GTPBP6 (11%-32%). Lung metastases differed from other metastatic sites (liver, stomach, and locoregional) in a higher frequency of nonsense mutations in the MH2 domain of SMAD4, oncodriver co-mutations, gains on chromosomes 2 and 20, CNV counts, and share of signature SBS5. Somatic alterations of KRAS in metastases (p=0.041) and MUC3A in both loci (p=0.041 and p=0.011, respectively) and CNVs count and size in metastases (p=0.024 and p=0.011) associated with response to systemic chemotherapy. Patients with mutated KRAS (p=0.045), high mutational load (p=0.004), and frequent CNVs (p=0.004) in metastatic loci had shortened survival after metastasis resection. Interestingly, the personalized-treatment targetable alterations, such as microsatellite instability and mismatch repair or homologous recombination deficiencies did not differ between the primary tumors and paired metastases or between the metastases from different secondary sites and had no prognostic value. The results suggest a potential prognostic role of KRAS mutations, mutation load, and CNVs in PDAC patients after metastasectomy and encourage further molecular profiling for personalized treatment of PDAC patients with different metastasis localization.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Laboratory Investigation
ISSN
0023-6837
e-ISSN
1530-0307
Volume of the periodical
105
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
104205
UT code for WoS article
001540319300001
EID of the result in the Scopus database
2-s2.0-105010609282