Browsing by Author "Chatterjee, Deyali"

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    Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications
    (BMJ Publishing Group, 2020-04-29) Luchini, Claudio; Brosens, Lodewijk A. A.; Wood, Laura D.; Chatterjee, Deyali; Shin, Jae Il; Sciammarella, Concetta; Fiadone, Giulia; Malleo, Giuseppe; Salvia, Roberto; Kryklyva, Valentyna; Piredda, Maria L.; Cheng, Liang; Lawlor, Rita T.; Adsay, Volkan; Scarpa, Aldo; Pathology and Laboratory Medicine, School of Medicine
    Objective Recently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC). Design PubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project). Results Overall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%–2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a KRAS/TP53 wild-type molecular background (p<0.01), with more common JAK genes mutations. Data on survival are still unclear. Conclusion PDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.
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    High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival
    (Springer Nature, 2023-10-19) Storrs, Erik P.; Chati, Prathamesh; Usmani, Abul; Sloan, Ian; Krasnick, Bradley A.; Babbra, Ramandeep; Harris, Peter K.; Sachs, Chloe M.; Qaium, Faridi; Chatterjee, Deyali; Wetzel, Chris; Goedegebuure, Peter; Hollander, Thomas; Anthony, Hephzibah; Ponce, Jennifer; Khaliq, Ateeq M.; Badiyan, Shahed; Kim, Hyun; Denardo, David G.; Lang, Gabriel D.; Cosgrove, Natalie D.; Kushnir, Vladimir M.; Early, Dayna S.; Masood, Ashiq; Lim, Kian-Huat; Hawkins, William G.; Ding, Li; Fields, Ryan C.; Das, Koushik K.; Chaudhuri, Aadel A.; Medicine, School of Medicine
    Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n = 25). We then combined these samples with surgical resection (n = 6) and publicly available samples to increase statistical power (n = 80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness, and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n = 268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens, including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.