Human Organoids Share Structural and Genetic Features with Primary Pancreatic Adenocarcinoma Tumors

Molecular Cancer Research : MCR
Isabel Romero-CalvoKevin P White

Abstract

Patient-derived pancreatic ductal adenocarcinoma (PDAC) organoid systems show great promise for understanding the biological underpinnings of disease and advancing therapeutic precision medicine. Despite the increased use of organoids, the fidelity of molecular features, genetic heterogeneity, and drug response to the tumor of origin remain important unanswered questions limiting their utility. To address this gap in knowledge, primary tumor- and patient-derived xenograft (PDX)-derived organoids, and 2D cultures for in-depth genomic and histopathologic comparisons with the primary tumor were created. Histopathologic features and PDAC representative protein markers (e.g., claudin 4 and CA19-9) showed strong concordance. DNA- and RNA-sequencing (RNAseq) of single organoids revealed patient-specific genomic and transcriptomic consistency. Single-cell RNAseq demonstrated that organoids are primarily a clonal population. In drug response assays, organoids displayed patient-specific sensitivities. In addition, the in vivo PDX response to FOLFIRINOX and gemcitabine/abraxane treatments were examined, which was recapitulated in vitro with organoids. This study has demonstrated that organoids are potentially invaluable for precision medi...Continue Reading

References

Sep 28, 2000·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·P ChuL M Weiss
Oct 29, 2003·Current Opinion in Biotechnology·Hynda K KleinmanMatthew P Hoffman
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Linda G Griffith, Melody A Swartz
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Nabeel BardeesyRonald A Depinho
Jun 27, 2006·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Aleksandr MorgulisRicha Agarwala
Aug 11, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Belen Rubio-ViqueiraManuel Hidalgo
Aug 9, 2007·Nature Reviews. Molecular Cell Biology·Francesco PampaloniErnst H K Stelzer
Jan 27, 2009·Biochimica Et Biophysica Acta·W C G van StaverenC Maenhaut
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
May 10, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Anna YemelyanovaRobert J Kurman
Oct 30, 2012·Nature·Andrew V BiankinSean M Grimmond
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Nov 20, 2012·Nature Methods·Adam Roberts, Lior Pachter
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
Sep 24, 2013·Nature Methods·Philip BrenneckeMarcus G Heisler
Oct 3, 2013·International Journal of Molecular Sciences·Antonio GnoniNicola Silvestris
Sep 11, 2014·The New England Journal of Medicine·David P RyanNabeel Bardeesy
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 6, 2015·Cell·Sylvia F BojDavid A Tuveson
Sep 19, 2015·Seminars in Radiation Oncology·Christopher D WilleyGeorge Yancey Gillespie
Jan 23, 2016·Nature Protocols·Jarno DrostHans Clevers
Feb 26, 2016·Nature·Peter BaileySean M Grimmond
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Oct 27, 2016·Nature Communications·Thierry JardéTrevor C Dale
Nov 18, 2016·Nature Protocols·Han FangGiuseppe Narzisi
Jan 6, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

❮ Previous
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Citations

Jun 30, 2019·Cancers·Giulia GaspariniMassimo Falconi
Oct 30, 2019·Journal of Mass Spectrometry : JMS·Jillian JohnsonLingjun Li
Dec 13, 2019·Current Diabetes Reports·Jeetindra R A BalakEelco J P de Koning
Aug 28, 2019·NPJ Precision Oncology·Lauren A HapachCynthia A Reinhart-King
Jun 6, 2020·Frontiers in Oncology·Joe T SharickMelissa C Skala
Mar 28, 2020·United European Gastroenterology Journal·Pierre-Olivier FrappartAlexander Kleger
Aug 23, 2020·Cancers·Annamaria MassaMassimo Aglietta
Oct 14, 2020·Journal of Cachexia, Sarcopenia and Muscle·Rianne D W VaesSander S Rensen
Oct 11, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Francisca BeatoJason B Fleming
Sep 30, 2020·JCI Insight·Ling HuangSenthil K Muthuswamy
Jan 8, 2021·Tissue Engineering. Part C, Methods·Vera M PietersAlison P McGuigan
Jan 26, 2021·Cellular Oncology (Dordrecht)·Axel BengtssonDaniel Ansari
Jan 7, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yiqi YuTaiping Zhang
Feb 23, 2021·Advanced Drug Delivery Reviews·Talia GolanMaria Raitses-Gurevich
May 4, 2021·International Journal of Nanomedicine·Julian PalzerAnjali A Roeth
Jul 18, 2021·Biomaterials·Yong Hun JungByung Soh Min
Jul 29, 2021·Cell Reports·Brian M LarsenAmeen A Salahudeen

❮ Previous
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