Genomic characterization of resectable pancreatic ductal adenocarcinoma (r-PDAC) on the NeoPancONE trial.
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774 Background: The optimal approach in r-PDAC remains unclear. Perioperative Modified FOLFIRINOX (mFFX) is increasingly used yet we lack biomarkers to guide this approach. NeoPancONE demonstrated GATA6 high expression at baseline and classical RNA subtype on resection tissue in pts receiving perioperative mFFX was associated with a trend toward improved EFS and OS. Low GATA6/basal-like predicts early disease progression and poor outcomes 1 . We now report on additional transcriptome and genomic subtypes identified in the NeoPancONE resection specimens. Methods: Patients with r-PDAC were enrolled following central review and underwent an EUS FNB for central analysis of baseline GATA6 by in-situ hybridization (ISH). Surgical resection specimens were processed in each centre and fresh frozen tumor tissue was transferred for central whole genome and transcriptome sequencing (WGTS) following laser capture microdissection. WGTS reports annotated mutations, copy number alterations, mutational signatures, and structural variant patterns. KRAS allelic states were reported with major imbalances in mutant KRAS (KRAS maj ) defined as mutant: Wildtype (WT) copy number ≥3. RNA transcriptomic subtypes (classical vs. basal-like) were classified by PurIST. We report a descriptive and survival analysis of the genomic subgroups. Results: Of the 84 enrolled baseline GATA6 ISH was analysed in 74 (88%); 81% high, 19% low and 73 (87%) proceeded to surgery. PurIST subtyping was available in 51 (70%) of resections; 86% classic, 14% basal. Spearman correlation coefficient between GATA6 ISH and RNA subtype = 0.51 (p<0.001). In those who recur/progress there was no association between GATA6 and RNA subtype and site of recurrence p=0.57 and p=0.18 respectively. WGS reports are available in 36 (49%) resections. KRASm were evident in 94% and KRAS G12D represented 50%. MTAP deletion was present in 22%, mostly correlated with CDKN2A deletions. Tumor suppressors TP53, CDKN2A and SMAD4 were lost in 86%, 69% and 50% respectively. KRAS maj was present in 8% of cases and polyploid tumors in 28%. Polyploid and KRAS major were enriched in the basal-like, and associated with significantly worse OS (p=0.046 and 0.0081 respectively). There was also enrichment of SMAD4 wt in basal-like tumors. ARID1A wt tumors demonstrated improved OS (P=0.032). Unstable genotypes were present in 6% with somatic-HRD evident in 3%. Conclusions: NeoPancONE represents a heterogeneous group of genotypes and molecular subgroups in r-PDAC. GATA6 low and basal-like subtype, associated with inferior outcomes, demonstrate less genomic stability. These results substantiate consideration of an alternative to mFFX based peri-operative therapy in GATA6 low/basal-like and reinforces the value of incorporating upfront genomic subtyping. Future r-PDAC trials should now incorporate RNA subtyping and KRAS directed therapies. Ref: 1. McLaughlin et al. ASCO 2025. Clinical trial information: NCT04472910 .
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Genomic characterization of resectable pancreatic ductal adenocarcinoma (r-PDAC) on the NeoPancONE trial.
- Date Crossref
- 10/01/2026
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University Health Network Division of Medical Oncology and Hematology pays non établi dans la noticeÉtablissement de santé
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University of Toronto Odette Cancer Centre pays non établi dans la noticeUniversité ou école supérieure
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Princess Margaret Cancer Centre pays non établi dans la noticeÉtablissement de santé
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Ontario Institute for Cancer Research PanCuRx Translational Research Initiative pays non établi dans la noticeOrganisme public
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Institute of Cancer Research pays non établi dans la noticeStructure de recherche
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Ottawa Hospital pays non établi dans la noticeÉtablissement de santé
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Sunnybrook Health Science Centre pays non établi dans la noticeÉtablissement de santé
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Health Sciences Centre pays non établi dans la noticeÉtablissement de santé
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Odette Cancer Centre pays non établi dans la noticeÉtablissement de santé
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Ottawa Hospital Research Institute pays non établi dans la noticeÉtablissement de santé
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Toronto General Hospital pays non établi dans la noticeÉtablissement de santé
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Department of Biostatistics pays non établi dans la noticeInstitution
Division of Medical Oncology and Hematology — University Health Network, Odette Cancer Centre — University of Toronto et Princess Margaret Cancer Centre, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.