Genomic analyses identify molecular subtypes of pancreatic cancer

Peter Bailey; David K. Chang; Katia Nones; Amber L. Johns; Ann-Marie Patch; Marie-Claude Gingras; David K. Miller; Angelika N. Christ; Neil D. Merrett; null [and ninety four others]

doi:10.1038/nature16965

Genomic analyses identify molecular subtypes of pancreatic cancer

Peter Bailey, David K. Chang, Katia Nones, Amber L. Johns, Ann-Marie Patch, Marie-Claude Gingras, David K. Miller, Angelika N. Christ, Neil D. Merrett, [and ninety four others]

Western Sydney University

Research output: Contribution to journal › Article › peer-review

2590 Citations (Scopus)

Abstract

Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63ΔN transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

Original language	English
Pages (from-to)	47-52
Number of pages	6
Journal	Nature
Volume	531
Issue number	7592
DOIs	https://doi.org/10.1038/nature16965
Publication status	Published - 2016

Keywords

cancer
genomics
pancreas

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature16965

Cite this

@article{844382c3b9aa448fa4e751a6791b7b4f,

title = "Genomic analyses identify molecular subtypes of pancreatic cancer",

abstract = "Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63ΔN transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.",

keywords = "cancer, genomics, pancreas",

author = "Peter Bailey and Chang, {David K.} and Katia Nones and Johns, {Amber L.} and Ann-Marie Patch and Marie-Claude Gingras and Miller, {David K.} and Christ, {Angelika N.} and Merrett, {Neil D.} and {[and ninety four others]}",

year = "2016",

doi = "10.1038/nature16965",

language = "English",

volume = "531",

pages = "47--52",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7592",

}

TY - JOUR

T1 - Genomic analyses identify molecular subtypes of pancreatic cancer

AU - Bailey, Peter

AU - Chang, David K.

AU - Nones, Katia

AU - Johns, Amber L.

AU - Patch, Ann-Marie

AU - Gingras, Marie-Claude

AU - Miller, David K.

AU - Christ, Angelika N.

AU - Merrett, Neil D.

AU - [and ninety four others], null

PY - 2016

Y1 - 2016

N2 - Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63ΔN transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

AB - Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63ΔN transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

KW - cancer

KW - genomics

KW - pancreas

UR - http://handle.uws.edu.au:8081/1959.7/uws:34220

U2 - 10.1038/nature16965

DO - 10.1038/nature16965

M3 - Article

SN - 0028-0836

VL - 531

SP - 47

EP - 52

JO - Nature

JF - Nature

IS - 7592

ER -

Genomic analyses identify molecular subtypes of pancreatic cancer

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this