@article{Wang:2017:10.1038/s41467-017-00992-9,
author = {Wang, H and Bender, A and Wang, P and Karakose, E and Inabnet, WB and Libutti, SK and Arnold, A and Lambertini, L and Stang, M and Chen, H and Kasai, Y and Mahajan, M and Kinoshita, Y and Fernandez-Ranvier, G and Becker, TC and Takane, KK and Walker, LA and Saul, S and Chen, R and Scott, DK and Ferrer, J and Antipin, Y and Donovan, M and Uzilov, AV and Reva, B and Schadt, EE and Losic, B and Argmann, C and Steward, AF},
doi = {10.1038/s41467-017-00992-9},
journal = {Nature Communications},
pages = {1--15},
title = {Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas},
url = {http://dx.doi.org/10.1038/s41467-017-00992-9},
volume = {8},
year = {2017}
}

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TY  - JOUR
AB  - Although diabetes results in part from a deficiency of normal pancreatic beta cells, inducing human beta cells to regenerate is difficult. Reasoning that insulinomas hold the “genomic recipe” for beta cell expansion, we surveyed 38 human insulinomas to obtain insights into therapeutic pathways for beta cell regeneration. An integrative analysis of whole-exome and RNA-sequencing data was employed to extensively characterize the genomic and molecular landscape of insulinomas relative to normal beta cells. Here, we show at the pathway level that the majority of the insulinomas display mutations, copy number variants and/or dysregulation of epigenetic modifying genes, most prominently in the polycomb and trithorax families. Importantly, these processes are coupled to co-expression network modules associated with cell proliferation, revealing candidates for inducing beta cell regeneration. Validation of key computational predictions supports the concept that understanding the molecular complexity of insulinoma may be a valuable approach to diabetes drug discovery.
AU  - Wang,H
AU  - Bender,A
AU  - Wang,P
AU  - Karakose,E
AU  - Inabnet,WB
AU  - Libutti,SK
AU  - Arnold,A
AU  - Lambertini,L
AU  - Stang,M
AU  - Chen,H
AU  - Kasai,Y
AU  - Mahajan,M
AU  - Kinoshita,Y
AU  - Fernandez-Ranvier,G
AU  - Becker,TC
AU  - Takane,KK
AU  - Walker,LA
AU  - Saul,S
AU  - Chen,R
AU  - Scott,DK
AU  - Ferrer,J
AU  - Antipin,Y
AU  - Donovan,M
AU  - Uzilov,AV
AU  - Reva,B
AU  - Schadt,EE
AU  - Losic,B
AU  - Argmann,C
AU  - Steward,AF
DO  - 10.1038/s41467-017-00992-9
EP  - 15
PY  - 2017///
SN  - 2041-1723
SP  - 1
TI  - Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-017-00992-9
UR  - https://www.nature.com/articles/s41467-017-00992-9
UR  - http://hdl.handle.net/10044/1/51586
VL  - 8
ER  - 

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