PuSH - Publication Server of Helmholtz Zentrum München: <em>Cdkn2a</em>-mutated pancreatic ductal organoids from induced pluripotent stem cells to model a cancer predisposition syndrome.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Merkle, J.* ; Breunig, M.* ; Schmid, M.* ; Allgöwer, C.* ; Krüger, J.* ; Melzer, M.K.* ; Bens, S.* ; Siebert, R.* ; Perkhofer, L.* ; Azoitei, N.* ; Seufferlein, T.* ; Heller, S.* ; Meier, M. ; Müller, M.* ; Kleger, A.* ; Hohwieler, M.*

Cdkn2a-mutated pancreatic ductal organoids from induced pluripotent stem cells to model a cancer predisposition syndrome.

Cancers 13:5139 (2021)

Publ. Version/Full Text

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

Patient-derived induced pluripotent stem cells (iPSCs) provide a unique platform to study hereditary disorders and predisposition syndromes by resembling germline mutations of affected individuals and by their potential to differentiate into nearly every cell type of the human body. We employed plucked human hair from two siblings with a family history of cancer carrying a pathogenic CDKN2A variant, P16-p.G101W/P14-p.R115L, to generate patient-specific iPSCs in a cancer-prone ancestry for downstream analytics. The differentiation capacity to pancreatic progenitors and to pancreatic duct-like organoids (PDLOs) according to a recently developed protocol remained unaffected. Upon inducible expression of KRASG12D using a piggyBac transposon system in CDKN2A-mutated PDLOs, we revealed structural and molecular changes in vitro, including disturbed polarity and epithelial-to-mesenchymal (EMT) transition. CDKN2A-mutated KRASG12D PDLO xenotransplants formed either a high-grade precancer lesion or a partially dedifferentiated PDAC-like tumor. Intriguingly, P14/P53/P21 and P16/RB cell-cycle checkpoint controls have been only partly overcome in these grafts, thereby still restricting the tumorous growth. Hereby, we provide a model for hereditary human pancreatic cancer that enables dissection of tumor initiation and early development starting from patient-specific CDKN2A-mutated pluripotent stem cells.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

6.639

1.292