Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

Kevin C Yang; Steve E Kalloger; John J Aird; Michael K C Lee; Christopher Rushton; Karen L Mungall; Andrew J Mungall; Dongxia Gao; Christine Chow; Jing Xu; Joanna M Karasinska; Shane Colborne; Steven J M Jones; Jörg Schrader; Ryan D Morin; Jonathan M Loree; Marco A Marra; Daniel J Renouf; Gregg B Morin; David F Schaeffer; Sharon M Gorski

doi:10.1016/j.celrep.2021.109817

Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

Standard

Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms. / Yang, Kevin C; Kalloger, Steve E; Aird, John J; Lee, Michael K C; Rushton, Christopher; Mungall, Karen L; Mungall, Andrew J; Gao, Dongxia; Chow, Christine; Xu, Jing; Karasinska, Joanna M; Colborne, Shane; Jones, Steven J M; Schrader, Jörg; Morin, Ryan D; Loree, Jonathan M; Marra, Marco A; Renouf, Daniel J; Morin, Gregg B; Schaeffer, David F; Gorski, Sharon M.

In: CELL REP, Vol. 37, No. 2, 109817, 12.10.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Yang, KC, Kalloger, SE, Aird, JJ, Lee, MKC, Rushton, C, Mungall, KL, Mungall, AJ, Gao, D, Chow, C, Xu, J, Karasinska, JM, Colborne, S, Jones, SJM, Schrader, J, Morin, RD, Loree, JM, Marra, MA, Renouf, DJ, Morin, GB, Schaeffer, DF & Gorski, SM 2021, 'Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms', CELL REP, vol. 37, no. 2, 109817. https://doi.org/10.1016/j.celrep.2021.109817

APA

Yang, K. C., Kalloger, S. E., Aird, J. J., Lee, M. K. C., Rushton, C., Mungall, K. L., Mungall, A. J., Gao, D., Chow, C., Xu, J., Karasinska, J. M., Colborne, S., Jones, S. J. M., Schrader, J., Morin, R. D., Loree, J. M., Marra, M. A., Renouf, D. J., Morin, G. B., ... Gorski, S. M. (2021). Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms. CELL REP, 37(2), [109817]. https://doi.org/10.1016/j.celrep.2021.109817

Vancouver

Yang KC, Kalloger SE, Aird JJ, Lee MKC, Rushton C, Mungall KL et al. Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms. CELL REP. 2021 Oct 12;37(2). 109817. https://doi.org/10.1016/j.celrep.2021.109817

Bibtex

@article{59e18e77f9524f49b3edb54482638a33,

title = "Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms",

abstract = "Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous. Here, we use a multi-omics approach to uncover the molecular factors underlying this heterogeneity. Transcriptomic analysis of 84 PNEN specimens, drawn from two cohorts, is substantiated with proteomic profiling and identifies four subgroups: Proliferative, PDX1-high, Alpha cell-like and Stromal/Mesenchymal. The Proliferative subgroup, consisting of both well- and poorly differentiated specimens, is associated with inferior overall survival probability. The PDX1-high and Alpha cell-like subgroups partially resemble previously described subtypes, and we further uncover distinctive metabolism-related features in the Alpha cell-like subgroup. The Stromal/Mesenchymal subgroup exhibits molecular characteristics of YAP1/WWTR1(TAZ) activation suggestive of Hippo signaling pathway involvement in PNENs. Whole-exome sequencing reveals subgroup-enriched mutational differences, supported by activity inference analysis, and identifies hypermorphic proto-oncogene variants in 14.3% of sequenced PNENs. Our study reveals differences in cellular signaling axes that provide potential directions for PNEN patient stratification and treatment strategies.",

author = "Yang, {Kevin C} and Kalloger, {Steve E} and Aird, {John J} and Lee, {Michael K C} and Christopher Rushton and Mungall, {Karen L} and Mungall, {Andrew J} and Dongxia Gao and Christine Chow and Jing Xu and Karasinska, {Joanna M} and Shane Colborne and Jones, {Steven J M} and J{\"o}rg Schrader and Morin, {Ryan D} and Loree, {Jonathan M} and Marra, {Marco A} and Renouf, {Daniel J} and Morin, {Gregg B} and Schaeffer, {David F} and Gorski, {Sharon M}",

year = "2021",

month = oct,

day = "12",

doi = "10.1016/j.celrep.2021.109817",

language = "English",

volume = "37",

journal = "CELL REP",

issn = "2211-1247",

publisher = "Elsevier",

number = "2",

}

RIS

TY - JOUR

T1 - Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms

AU - Yang, Kevin C

AU - Kalloger, Steve E

AU - Aird, John J

AU - Lee, Michael K C

AU - Rushton, Christopher

AU - Mungall, Karen L

AU - Mungall, Andrew J

AU - Gao, Dongxia

AU - Chow, Christine

AU - Xu, Jing

AU - Karasinska, Joanna M

AU - Colborne, Shane

AU - Jones, Steven J M

AU - Schrader, Jörg

AU - Morin, Ryan D

AU - Loree, Jonathan M

AU - Marra, Marco A

AU - Renouf, Daniel J

AU - Morin, Gregg B

AU - Schaeffer, David F

AU - Gorski, Sharon M

PY - 2021/10/12

Y1 - 2021/10/12

N2 - Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous. Here, we use a multi-omics approach to uncover the molecular factors underlying this heterogeneity. Transcriptomic analysis of 84 PNEN specimens, drawn from two cohorts, is substantiated with proteomic profiling and identifies four subgroups: Proliferative, PDX1-high, Alpha cell-like and Stromal/Mesenchymal. The Proliferative subgroup, consisting of both well- and poorly differentiated specimens, is associated with inferior overall survival probability. The PDX1-high and Alpha cell-like subgroups partially resemble previously described subtypes, and we further uncover distinctive metabolism-related features in the Alpha cell-like subgroup. The Stromal/Mesenchymal subgroup exhibits molecular characteristics of YAP1/WWTR1(TAZ) activation suggestive of Hippo signaling pathway involvement in PNENs. Whole-exome sequencing reveals subgroup-enriched mutational differences, supported by activity inference analysis, and identifies hypermorphic proto-oncogene variants in 14.3% of sequenced PNENs. Our study reveals differences in cellular signaling axes that provide potential directions for PNEN patient stratification and treatment strategies.

AB - Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous. Here, we use a multi-omics approach to uncover the molecular factors underlying this heterogeneity. Transcriptomic analysis of 84 PNEN specimens, drawn from two cohorts, is substantiated with proteomic profiling and identifies four subgroups: Proliferative, PDX1-high, Alpha cell-like and Stromal/Mesenchymal. The Proliferative subgroup, consisting of both well- and poorly differentiated specimens, is associated with inferior overall survival probability. The PDX1-high and Alpha cell-like subgroups partially resemble previously described subtypes, and we further uncover distinctive metabolism-related features in the Alpha cell-like subgroup. The Stromal/Mesenchymal subgroup exhibits molecular characteristics of YAP1/WWTR1(TAZ) activation suggestive of Hippo signaling pathway involvement in PNENs. Whole-exome sequencing reveals subgroup-enriched mutational differences, supported by activity inference analysis, and identifies hypermorphic proto-oncogene variants in 14.3% of sequenced PNENs. Our study reveals differences in cellular signaling axes that provide potential directions for PNEN patient stratification and treatment strategies.

U2 - 10.1016/j.celrep.2021.109817

DO - 10.1016/j.celrep.2021.109817

M3 - SCORING: Journal article

C2 - 34644566

VL - 37

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 2

M1 - 109817

ER -