Genomic analyses identify molecular subtypes of pancreatic cancer

P. Bailey; D. K. Chang; K. Nones; A. L. Johns; Patch A. -M.; Gingras M. -C.; D. K. Miller; A. N. Christ; T. J. C. Bruxner; M. C. Quinn; C. Nourse; L. C. Murtaugh; I. Harliwong; S. Idrisoglu; S. Manning; E. Nourbakhsh; S. Wani; L. Fink; O. Holmes; V. Chin; M. J. Anderson; S. Kazakoff; C. Leonard; F. Newell; N. Waddell; S. Wood; Q. Xu; P. J. Wilson; N. Cloonan; K. S. Kassahn; D. Taylor; K. Quek; A. Robertson; L. Pantano; L. Mincarelli; L. N. Sanchez; L. Evers; J. Wu; M. Pinese; M. J. Cowley; M. D. Jones; E. K. Colvin; A. M. Nagrial; E. S. Humphrey; L. A. Chantrill; A. Mawson; J. Humphris; A. Chou; M. Pajic; C. J. Scarlett; A. V. Pinho; M. Giry-Laterriere; I. Rooman; J. S. Samra; J. G. Kench; J. A. Lovell; N. D. Merrett; C. W. Toon; K. Epari; N. Q. Nguyen; A. Barbour; N. Zeps; K. Moran-Jones; N. B. Jamieson; J. S. Graham; F. Duthie; K. Oien; J. Hair; R. Grutzmann; A. Maitra; C. A. Iacobuzio-Donahue; C. L. Wolfgang; R. A. Morgan; R. T. Lawlor; V. Corbo; C. Bassi; B. Rusev; P. Capelli; R. Salvia; Giampaolo Tortora; D. Mukhopadhyay; G. M. Petersen; D. M. Munzy; W. E. Fisher; S. A. Karim; J. R. Eshleman; R. H. Hruban; C. Pilarsky; J. P. Morton; O. J. Sansom; A. Scarpa; E. A. Musgrove; U. -M. H. Bailey; O. Hofmann; R. L. Sutherland; D. A. Wheeler; A. J. Gill; R. A. Gibbs; J. V. Pearson; N. Waddell; A. V. Biankin; S. M. Grimmond

doi:10.1038/nature16965

Genomic analyses identify molecular subtypes of pancreatic cancer

P. Bailey
, D. K. Chang
, K. Nones
, A. L. Johns
, Patch A. -M.
, Gingras M. -C.
, D. K. Miller
, A. N. Christ
, T. J. C. Bruxner
, M. C. Quinn
, C. Nourse
, L. C. Murtaugh
, I. Harliwong
, S. Idrisoglu
, S. Manning
, E. Nourbakhsh
, S. Wani
, L. Fink
, O. Holmes
, V. Chin

M. J. Anderson, S. Kazakoff, C. Leonard, F. Newell, N. Waddell, S. Wood, Q. Xu, P. J. Wilson, N. Cloonan, K. S. Kassahn, D. Taylor, K. Quek, A. Robertson, L. Pantano, L. Mincarelli, L. N. Sanchez, L. Evers, J. Wu, M. Pinese, M. J. Cowley, M. D. Jones, E. K. Colvin, A. M. Nagrial, E. S. Humphrey, L. A. Chantrill, A. Mawson, J. Humphris, A. Chou, M. Pajic, C. J. Scarlett, A. V. Pinho, M. Giry-Laterriere, I. Rooman, J. S. Samra, J. G. Kench, J. A. Lovell, N. D. Merrett, C. W. Toon, K. Epari, N. Q. Nguyen, A. Barbour, N. Zeps, K. Moran-Jones, N. B. Jamieson, J. S. Graham, F. Duthie, K. Oien, J. Hair, R. Grutzmann, A. Maitra, C. A. Iacobuzio-Donahue, C. L. Wolfgang, R. A. Morgan, R. T. Lawlor, V. Corbo, C. Bassi, B. Rusev, P. Capelli, R. Salvia, Giampaolo Tortora, D. Mukhopadhyay, G. M. Petersen, D. M. Munzy, W. E. Fisher, S. A. Karim, J. R. Eshleman, R. H. Hruban, C. Pilarsky, J. P. Morton, O. J. Sansom, A. Scarpa, E. A. Musgrove, U. -M. H. Bailey, O. Hofmann, R. L. Sutherland, D. A. Wheeler, A. J. Gill, R. A. Gibbs, J. V. Pearson, N. Waddell, A. V. Biankin^*, S. M. Grimmond

^*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivista › Articolo

1336 Citazioni (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.

Lingua originale	Inglese
pagine (da-a)	47-52
Numero di pagine	6
Rivista	Nature
Volume	531
Numero di pubblicazione	7592
DOI	https://doi.org/10.1038/nature16965
Stato di pubblicazione	Pubblicato - 2016

All Science Journal Classification (ASJC) codes

Multidisciplinare

Keywords

Animals
Basic Helix-Loop-Helix Transcription Factors
Carcinoma
Cell Line
Cytoplasmic and Nuclear
DNA Methylation
DNA-Binding Proteins
Gene Expression Regulation
Gene Regulatory Networks
Genes
Genetic
Genome
Genomics
Hepatocyte Nuclear Factor 3-beta
Hepatocyte Nuclear Factor 3-gamma
Histone Demethylases
Homeodomain Proteins
Human
Humans
Mice
Mutation
Neoplasm
Neoplastic
Nuclear Proteins
Pancreatic Ductal
Pancreatic Neoplasms
Prognosis
Receptors
Survival Analysis
Trans-Activators
Transcription
Transcription Factors
Transcriptome
Tumor
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
Zebrafish Proteins

OSS delle Nazioni Unite

Questo processo contribuisce al raggiungimento dei seguenti obiettivi di sviluppo sostenibile

Accesso al documento

10.1038/nature16965

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Bailey, P., Chang, D. K., Nones, K., Johns, A. L., -M., P. A., -C., G. M., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., Nourse, C., Murtaugh, L. C., Harliwong, I., Idrisoglu, S., Manning, S., Nourbakhsh, E., Wani, S., Fink, L., Holmes, O., ... Grimmond, S. M. (2016). Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 531(7592), 47-52. https://doi.org/10.1038/nature16965

@article{a8e7d5e051a14380b1a489ff30cd7353,

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 = "Animals, Basic Helix-Loop-Helix Transcription Factors, Carcinoma, Cell Line, Cytoplasmic and Nuclear, DNA Methylation, DNA-Binding Proteins, Gene Expression Regulation, Gene Regulatory Networks, Genes, Genetic, Genome, Genomics, Hepatocyte Nuclear Factor 3-beta, Hepatocyte Nuclear Factor 3-gamma, Histone Demethylases, Homeodomain Proteins, Human, Humans, Mice, Mutation, Neoplasm, Neoplastic, Nuclear Proteins, Pancreatic Ductal, Pancreatic Neoplasms, Prognosis, Receptors, Survival Analysis, Trans-Activators, Transcription, Transcription Factors, Transcriptome, Tumor, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Zebrafish Proteins, Animals, Basic Helix-Loop-Helix Transcription Factors, Carcinoma, Cell Line, Cytoplasmic and Nuclear, DNA Methylation, DNA-Binding Proteins, Gene Expression Regulation, Gene Regulatory Networks, Genes, Genetic, Genome, Genomics, Hepatocyte Nuclear Factor 3-beta, Hepatocyte Nuclear Factor 3-gamma, Histone Demethylases, Homeodomain Proteins, Human, Humans, Mice, Mutation, Neoplasm, Neoplastic, Nuclear Proteins, Pancreatic Ductal, Pancreatic Neoplasms, Prognosis, Receptors, Survival Analysis, Trans-Activators, Transcription, Transcription Factors, Transcriptome, Tumor, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Zebrafish Proteins",

author = "P. Bailey and Chang, \{D. K.\} and K. Nones and Johns, \{A. L.\} and -M., \{Patch A.\} and -C., \{Gingras M.\} and Miller, \{D. K.\} and Christ, \{A. N.\} and Bruxner, \{T. J. C.\} and Quinn, \{M. C.\} and C. Nourse and Murtaugh, \{L. C.\} and I. Harliwong and S. Idrisoglu and S. Manning and E. Nourbakhsh and S. Wani and L. Fink and O. Holmes and V. Chin and Anderson, \{M. J.\} and S. Kazakoff and C. Leonard and F. Newell and N. Waddell and S. Wood and Q. Xu and Wilson, \{P. J.\} and N. Cloonan and Kassahn, \{K. S.\} and D. Taylor and K. Quek and A. Robertson and L. Pantano and L. Mincarelli and Sanchez, \{L. N.\} and L. Evers and J. Wu and M. Pinese and Cowley, \{M. J.\} and Jones, \{M. D.\} and Colvin, \{E. K.\} and Nagrial, \{A. M.\} and Humphrey, \{E. S.\} and Chantrill, \{L. A.\} and A. Mawson and J. Humphris and A. Chou and M. Pajic and Scarlett, \{C. J.\} and Pinho, \{A. V.\} and M. Giry-Laterriere and I. Rooman and Samra, \{J. S.\} and Kench, \{J. G.\} and Lovell, \{J. A.\} and Merrett, \{N. D.\} and Toon, \{C. W.\} and K. Epari and Nguyen, \{N. Q.\} and A. Barbour and N. Zeps and K. Moran-Jones and Jamieson, \{N. B.\} and Graham, \{J. S.\} and F. Duthie and K. Oien and J. Hair and R. Grutzmann and A. Maitra and Iacobuzio-Donahue, \{C. A.\} and Wolfgang, \{C. L.\} and Morgan, \{R. A.\} and Lawlor, \{R. T.\} and V. Corbo and C. Bassi and B. Rusev and P. Capelli and R. Salvia and Giampaolo Tortora and D. Mukhopadhyay and Petersen, \{G. M.\} and Munzy, \{D. M.\} and Fisher, \{W. E.\} and Karim, \{S. A.\} and Eshleman, \{J. R.\} and Hruban, \{R. H.\} and C. Pilarsky and Morton, \{J. P.\} and Sansom, \{O. J.\} and A. Scarpa and Musgrove, \{E. A.\} and Bailey, \{U. -M. H.\} and O. Hofmann and Sutherland, \{R. L.\} and Wheeler, \{D. A.\} and Gill, \{A. J.\} and Gibbs, \{R. A.\} and Pearson, \{J. V.\} and N. Waddell and Biankin, \{A. V.\} and Grimmond, \{S. M.\}",

year = "2016",

doi = "10.1038/nature16965",

language = "English",

volume = "531",

pages = "47--52",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7592",

}

Bailey, P, Chang, DK, Nones, K, Johns, AL, -M., PA, -C., GM, Miller, DK, Christ, AN, Bruxner, TJC, Quinn, MC, Nourse, C, Murtaugh, LC, Harliwong, I, Idrisoglu, S, Manning, S, Nourbakhsh, E, Wani, S, Fink, L, Holmes, O, Chin, V, Anderson, MJ, Kazakoff, S, Leonard, C, Newell, F, Waddell, N, Wood, S, Xu, Q, Wilson, PJ, Cloonan, N, Kassahn, KS, Taylor, D, Quek, K, Robertson, A, Pantano, L, Mincarelli, L, Sanchez, LN, Evers, L, Wu, J, Pinese, M, Cowley, MJ, Jones, MD, Colvin, EK, Nagrial, AM, Humphrey, ES, Chantrill, LA, Mawson, A, Humphris, J, Chou, A, Pajic, M, Scarlett, CJ, Pinho, AV, Giry-Laterriere, M, Rooman, I, Samra, JS, Kench, JG, Lovell, JA, Merrett, ND, Toon, CW, Epari, K, Nguyen, NQ, Barbour, A, Zeps, N, Moran-Jones, K, Jamieson, NB, Graham, JS, Duthie, F, Oien, K, Hair, J, Grutzmann, R, Maitra, A, Iacobuzio-Donahue, CA, Wolfgang, CL, Morgan, RA, Lawlor, RT, Corbo, V, Bassi, C, Rusev, B, Capelli, P, Salvia, R, Tortora, G, Mukhopadhyay, D, Petersen, GM, Munzy, DM, Fisher, WE, Karim, SA, Eshleman, JR, Hruban, RH, Pilarsky, C, Morton, JP, Sansom, OJ, Scarpa, A, Musgrove, EA, Bailey, U-MH, Hofmann, O, Sutherland, RL, Wheeler, DA, Gill, AJ, Gibbs, RA, Pearson, JV, Waddell, N, Biankin, AV & Grimmond, SM 2016, 'Genomic analyses identify molecular subtypes of pancreatic cancer', Nature, vol. 531, n. 7592, pagg. 47-52. https://doi.org/10.1038/nature16965

TY - JOUR

T1 - Genomic analyses identify molecular subtypes of pancreatic cancer

AU - Bailey, P.

AU - Chang, D. K.

AU - Nones, K.

AU - Johns, A. L.

AU - -M., Patch A.

AU - -C., Gingras M.

AU - Miller, D. K.

AU - Christ, A. N.

AU - Bruxner, T. J. C.

AU - Quinn, M. C.

AU - Nourse, C.

AU - Murtaugh, L. C.

AU - Harliwong, I.

AU - Idrisoglu, S.

AU - Manning, S.

AU - Nourbakhsh, E.

AU - Wani, S.

AU - Fink, L.

AU - Holmes, O.

AU - Chin, V.

AU - Anderson, M. J.

AU - Kazakoff, S.

AU - Leonard, C.

AU - Newell, F.

AU - Waddell, N.

AU - Wood, S.

AU - Xu, Q.

AU - Wilson, P. J.

AU - Cloonan, N.

AU - Kassahn, K. S.

AU - Taylor, D.

AU - Quek, K.

AU - Robertson, A.

AU - Pantano, L.

AU - Mincarelli, L.

AU - Sanchez, L. N.

AU - Evers, L.

AU - Wu, J.

AU - Pinese, M.

AU - Cowley, M. J.

AU - Jones, M. D.

AU - Colvin, E. K.

AU - Nagrial, A. M.

AU - Humphrey, E. S.

AU - Chantrill, L. A.

AU - Mawson, A.

AU - Humphris, J.

AU - Chou, A.

AU - Pajic, M.

AU - Scarlett, C. J.

AU - Pinho, A. V.

AU - Giry-Laterriere, M.

AU - Rooman, I.

AU - Samra, J. S.

AU - Kench, J. G.

AU - Lovell, J. A.

AU - Merrett, N. D.

AU - Toon, C. W.

AU - Epari, K.

AU - Nguyen, N. Q.

AU - Barbour, A.

AU - Zeps, N.

AU - Moran-Jones, K.

AU - Jamieson, N. B.

AU - Graham, J. S.

AU - Duthie, F.

AU - Oien, K.

AU - Hair, J.

AU - Grutzmann, R.

AU - Maitra, A.

AU - Iacobuzio-Donahue, C. A.

AU - Wolfgang, C. L.

AU - Morgan, R. A.

AU - Lawlor, R. T.

AU - Corbo, V.

AU - Bassi, C.

AU - Rusev, B.

AU - Capelli, P.

AU - Salvia, R.

AU - Tortora, Giampaolo

AU - Mukhopadhyay, D.

AU - Petersen, G. M.

AU - Munzy, D. M.

AU - Fisher, W. E.

AU - Karim, S. A.

AU - Eshleman, J. R.

AU - Hruban, R. H.

AU - Pilarsky, C.

AU - Morton, J. P.

AU - Sansom, O. J.

AU - Scarpa, A.

AU - Musgrove, E. A.

AU - Bailey, U. -M. H.

AU - Hofmann, O.

AU - Sutherland, R. L.

AU - Wheeler, D. A.

AU - Gill, A. J.

AU - Gibbs, R. A.

AU - Pearson, J. V.

AU - Waddell, N.

AU - Biankin, A. V.

AU - Grimmond, S. M.

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 - Animals

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Carcinoma

KW - Cell Line

KW - Cytoplasmic and Nuclear

KW - DNA Methylation

KW - DNA-Binding Proteins

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Genes

KW - Genetic

KW - Genome

KW - Genomics

KW - Hepatocyte Nuclear Factor 3-beta

KW - Hepatocyte Nuclear Factor 3-gamma

KW - Histone Demethylases

KW - Homeodomain Proteins

KW - Human

KW - Humans

KW - Mice

KW - Mutation

KW - Neoplasm

KW - Neoplastic

KW - Nuclear Proteins

KW - Pancreatic Ductal

KW - Pancreatic Neoplasms

KW - Prognosis

KW - Receptors

KW - Survival Analysis

KW - Trans-Activators

KW - Transcription

KW - Transcription Factors

KW - Transcriptome

KW - Tumor

KW - Tumor Suppressor Protein p53

KW - Tumor Suppressor Proteins

KW - Zebrafish Proteins

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Carcinoma

KW - Cell Line

KW - Cytoplasmic and Nuclear

KW - DNA Methylation

KW - DNA-Binding Proteins

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Genes

KW - Genetic

KW - Genome

KW - Genomics

KW - Hepatocyte Nuclear Factor 3-beta

KW - Hepatocyte Nuclear Factor 3-gamma

KW - Histone Demethylases

KW - Homeodomain Proteins

KW - Human

KW - Humans

KW - Mice

KW - Mutation

KW - Neoplasm

KW - Neoplastic

KW - Nuclear Proteins

KW - Pancreatic Ductal

KW - Pancreatic Neoplasms

KW - Prognosis

KW - Receptors

KW - Survival Analysis

KW - Trans-Activators

KW - Transcription

KW - Transcription Factors

KW - Transcriptome

KW - Tumor

KW - Tumor Suppressor Protein p53

KW - Tumor Suppressor Proteins

KW - Zebrafish Proteins

UR - https://publicatt.unicatt.it/handle/10807/172586

UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84960194345&origin=inward

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84960194345&origin=inward

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

All Science Journal Classification (ASJC) codes

Keywords

OSS delle Nazioni Unite

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