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dc.contributor.authorFrizziero, Melissa
dc.contributor.authorKilgour, Elaine
dc.contributor.authorSimpson, Kathryn L
dc.contributor.authorRothwell, Dominic G|Frese, Kristopher K
dc.contributor.authorChen, Y.
dc.contributor.authorKerr, Alastair
dc.contributor.authorLamarca, Angela
dc.contributor.authorHubner, Richard A
dc.contributor.authorValle, Juan W
dc.contributor.authorMcNamara, Mairead G
dc.contributor.authorDive, Caroline
dc.date.accessioned2022-05-26T08:34:56Z
dc.date.available2022-05-26T08:34:56Z
dc.date.issued2022en
dc.identifier.citationFrizziero M, Kilgour E, Simpson KL, Rothwell D, Frese K, Chen Y, et al. The first circulating tumor cell-derived explant (CDX) model of a Merkel cell carcinoma. Journal of Neuroendocrinology. 2022;34:41.en
dc.identifier.urihttp://hdl.handle.net/10541/625209
dc.description.abstractIntroduction:Poorly differentiated ExtraPulmonary NeuroEndocrine Carcinomas (EP-NECs) have a median overall survival of <12 months and lack effective treatments; patient-relevant preclinical models are needed. Aim(s):In EP-NEC, to assess feasibility of liquid biopsy technologies used for the pulmonary-NEC counterpart Small Cell Lung Cancer (SCLC); circulating tumor cell (CTC) enumeration by CellSearch (CS) and CTC-Derived eXplants (CDX) which in SCLC mirror biology and chemo response of donor patients. Materials and methods:Serial CTC enumeration and attempt at CDX generation in a prospective cohort of patients with advanced EP-NEC undergoing palliative chemotherapy (chemo). Results:27 patients were recruited from Jun-19 to Nov-21. CS-CTCs were present in 70% of pre-chemo samples (mean 57, median 2, range 0-685 CTCs per 7.5mL of blood). A CDX was generated with a pre-chemo sample from a patient with a NEC of unknown origin. Whole-exome sequencing of the CDX and matched pre-chemo cell-free DNA from the donor revealed shared copy number changes and somatic mutations (e.g. PIK3CA). The CDX was sensitive to platinum/etoposide in vivo, mirroring the donor’s treatment response. Morphological and immunohistochemical (IHC) evaluation of the CDX showed a small cell NEC concordant withthe donor’s biopsy. Further IHC and RNA sequencing revealed expression of the neuroendocrine transcription factor atonal homolog 1 (ATOH1), CK20 and abundant Merkel cell polyomavirus transcripts; prompting reclassification of the diagnosis to Merkel cell carcinoma (MCC). Conclusion:This is the first reported MCC CDX and provides an avatar for in-depth molecular characterisation of the original tumor, with potential to inform future treatment for the donor (alive >24 months from diagnosis) and future patients.en
dc.language.isoenen
dc.titleThe first circulating tumor cell-derived explant (CDX) model of a Merkel cell carcinomaen
dc.typeMeetings and Proceedingsen
dc.contributor.departmentCancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Manchester,en
dc.identifier.journalJournal of Neuroendocrinologyen
dc.description.noteen]


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