Clinical utility of plasma cell-free DNA in pancreatic neuroendocrine neoplasms

In advanced pancreatic neuroendocrine neoplasms (PanNEN), there are little data detailing the frequency of genetic alterations identified in cell free DNA (cfDNA), plasma-tissue concordance of detected alterations, and clinical utility of cfDNA. Patients with metastatic PanNENs underwent cfDNA colle...

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Vydáno v:Endocrine-related cancer Ročník 31; číslo 4
Hlavní autoři: Cowzer, Darren, Shah, Ronak H, Chou, Joanne F, Kundra, Ritika, Punn, Sippy, Fiedler, Laura, DeMore, April, Capanu, Marinela, Berger, Michael F, Reidy-Lagunes, Diane, Raj, Nitya
Médium: Journal Article
Jazyk:angličtina
Vydáno: England 01.04.2024
Témata:
Cell-Free Nucleic Acids - genetics
Genome
Genomics
High-Throughput Nucleotide Sequencing
Humans
Mutation
Neuroendocrine Tumors - genetics
Pancreatic Neoplasms - genetics
cell-free DNA
precision oncology
circulating-tumor DNA
pancreatic neuroendocrine neoplasms
next generation sequencing
ISSN:1479-6821, 1479-6821
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Shrnutí:In advanced pancreatic neuroendocrine neoplasms (PanNEN), there are little data detailing the frequency of genetic alterations identified in cell free DNA (cfDNA), plasma-tissue concordance of detected alterations, and clinical utility of cfDNA. Patients with metastatic PanNENs underwent cfDNA collection in routine practice. Next-generation sequencing (NGS) of cfDNA and matched tissue when available was performed. Clinical actionability of variants was annotated by OncoKB. Thirty-two cfDNA samples were analyzed from 25 patients, the majority who had well-differentiated intermediate grade disease (13/25; 52%). Genomic alterations were detected in 68% of patients and in 66% of all cfDNA samples. The most frequently altered genes were DAXX (28%), TSC2 (24%), MEN1 (24%), ARID1B (20%), ARID1A (12%), and ATRX (12%). Twenty-three out of 25 (92%) patients underwent tumor tissue NGS. Tissue-plasma concordance for select genes was as follows:DAXX (95.7%), ARID1A (91.1%), ATRX (87%), TSC2 (82.6%), MEN1 (69.6%). Potentially actionable alterations were identified in cfDNA of 8 patients, including TSC2 (4; level 3b), ATM (1; level 3b), ARID1A (2; level 4), and KRAS (1; level 4). An ETV6:NTRK fusion detected in tumor tissue was treated with larotrectinib; at progression, sequencing of cfDNA identified an NTRK3 G623R alteration as the acquired mechanism of resistance; the patient enrolled in a clinical trial of a second-generation TRK inhibitor with clinical benefit. In metastatic PanNENs, cfDNA-based NGS identified tumor-associated mutations in 66% of plasma samples with a high level of plasma-tissue agreement in PanNEN-associated genes. Clonal evolution, actionable alterations, and resistance mechanisms were detected through circulating cfDNA genotyping.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1479-6821
1479-6821
DOI:10.1530/ERC-23-0292