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Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number chan... Full description

Journal Title: Cell April 5, 2018, Vol.173(2), pp.321-337.e10
Main Author: Sanchez-Vega, Francisco
Other Authors: Mina, Marco , Armenia, Joshua , Chatila, Walid K , Luna, Augustin , La, Konnor C , Dimitriadoy, Sofia , Liu, David L , Kantheti, Havish S , Saghafinia, Sadegh , Chakravarty, Debyani , Daian, Foysal , Gao, Qingsong , Bailey, Matthew H , Liang, Wen-Wei , Foltz, Steven M , Shmulevich, Ilya , Ding, Li , Heins, Zachary , Ochoa
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1097-4172 ; DOI: 10.1016/j.cell.2018.03.035
Link: http://search.proquest.com/docview/2022978598/?pq-origsite=primo
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title: Oncogenic Signaling Pathways in The Cancer Genome Atlas.
format: Article
creator:
  • Sanchez-Vega, Francisco
  • Mina, Marco
  • Armenia, Joshua
  • Chatila, Walid K
  • Luna, Augustin
  • La, Konnor C
  • Dimitriadoy, Sofia
  • Liu, David L
  • Kantheti, Havish S
  • Saghafinia, Sadegh
  • Chakravarty, Debyani
  • Daian, Foysal
  • Gao, Qingsong
  • Bailey, Matthew H
  • Liang, Wen-Wei
  • Foltz, Steven M
  • Shmulevich, Ilya
  • Ding, Li
  • Heins, Zachary
  • Ochoa
subjects:
  • Databases, Genetic–Genetics
  • Genes, Neoplasm–Pathology
  • Humans–Genetics
  • Neoplasms–Metabolism
  • Phosphatidylinositol 3-Kinases–Genetics
  • Signal Transduction–Genetics
  • Transforming Growth Factor Beta–Metabolism
  • Tumor Suppressor Protein P53–Genetics
  • Wnt Proteins–Metabolism
  • Wnt Proteins–Genetics
  • Wnt Proteins–Metabolism
  • Transforming Growth Factor Beta
  • Tumor Suppressor Protein P53
  • Wnt Proteins
  • Phosphatidylinositol 3-Kinases
  • Pancanatlas
  • Tcga
  • Cancer Genome Atlas
  • Cancer Genomics
  • Combination Therapy
ispartof: Cell, April 5, 2018, Vol.173(2), pp.321-337.e10
description: Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. •Alteration map of 10 signaling pathways across 9,125 samples from 33 cancer types•Reusable, curated pathway templates that include a catalogue of driver genes•57% of tumors have at least one potentially actionable alteration in these pathways•Co-occurrence of actionable alterations suggests combination therapy opportunities An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies.
language: eng
source:
identifier: E-ISSN: 1097-4172 ; DOI: 10.1016/j.cell.2018.03.035
fulltext: fulltext
issn:
  • 10974172
  • 1097-4172
url: Link


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titleOncogenic Signaling Pathways in The Cancer Genome Atlas.
creatorSanchez-Vega, Francisco ; Mina, Marco ; Armenia, Joshua ; Chatila, Walid K ; Luna, Augustin ; La, Konnor C ; Dimitriadoy, Sofia ; Liu, David L ; Kantheti, Havish S ; Saghafinia, Sadegh ; Chakravarty, Debyani ; Daian, Foysal ; Gao, Qingsong ; Bailey, Matthew H ; Liang, Wen-Wei ; Foltz, Steven M ; Shmulevich, Ilya ; Ding, Li ; Heins, Zachary ; Ochoa
contributorCaesar-Johnson, Samantha J (correspondence author) ; Demchok, John A (record owner) ; Felau, Ina ; Kasapi, Melpomeni ; Ferguson, Martin L ; Hutter, Carolyn M ; Sofia, Heidi J ; Tarnuzzer, Roy ; Wang, Zhining ; Yang, Liming ; Zenklusen, Jean C ; Zhang, Jiashan Julia ; Chudamani, Sudha ; Liu, Jia ; Lolla, Laxmi ; Naresh, Rashi ; Pihl, Todd ; Sun, Qiang ; Wan, Yunhu ; Wu
ispartofCell, April 5, 2018, Vol.173(2), pp.321-337.e10
identifierE-ISSN: 1097-4172 ; DOI: 10.1016/j.cell.2018.03.035
subjectDatabases, Genetic–Genetics ; Genes, Neoplasm–Pathology ; Humans–Genetics ; Neoplasms–Metabolism ; Phosphatidylinositol 3-Kinases–Genetics ; Signal Transduction–Genetics ; Transforming Growth Factor Beta–Metabolism ; Tumor Suppressor Protein P53–Genetics ; Wnt Proteins–Metabolism ; Wnt Proteins–Genetics ; Wnt Proteins–Metabolism ; Transforming Growth Factor Beta ; Tumor Suppressor Protein P53 ; Wnt Proteins ; Phosphatidylinositol 3-Kinases ; Pancanatlas ; Tcga ; Cancer Genome Atlas ; Cancer Genomics ; Combination Therapy
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descriptionGenetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy. •Alteration map of 10 signaling pathways across 9,125 samples from 33 cancer types•Reusable, curated pathway templates that include a catalogue of driver genes•57% of tumors have at least one potentially actionable alteration in these pathways•Co-occurrence of actionable alterations suggests combination therapy opportunities An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies.
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47Mccormick, Frank
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49Van Allen, Eliezer M
50Cherniack, Andrew D
51Ciriello, Giovanni
52Sander, Chris
53Schultz, Nikolaus
titleOncogenic Signaling Pathways in The Cancer Genome Atlas.
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0Databases, Genetic–Genetics
1Genes, Neoplasm–Pathology
2Humans–Genetics
3Neoplasms–Metabolism
4Phosphatidylinositol 3-Kinases–Genetics
5Signal Transduction–Genetics
6Transforming Growth Factor Beta–Metabolism
7Tumor Suppressor Protein P53–Genetics...
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19Wu, Ye
20Cho, Juok
21Defreitas, Timothy
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24Getz, Gad
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26Kim, Jaegil
27Lawrence, Michael S
28Lin, Pei
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31Saksena, Gordon
32Voet, Doug
33Zhang, Hailei
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36Dhankani, Varsha
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38Kramer, Roger
39Leinonen, Kalle
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81Sander, Chris
82Schultz, Nikolaus
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89Anur, Pavana
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96Hayes, D Neil
97Parker, Joel S
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99Ally, Adrian
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titleOncogenic Signaling Pathways in The Cancer Genome Atlas.
authorSanchez-Vega, Francisco ; Mina, Marco ; Armenia, Joshua ; Chatila, Walid K ; Luna, Augustin ; La, Konnor C ; Dimitriadoy, Sofia ; Liu, David L ; Kantheti, Havish S ; Saghafinia, Sadegh ; Chakravarty, Debyani ; Daian, Foysal ; Gao, Qingsong ; Bailey, Matthew...
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4Phosphatidylinositol 3-Kinases–Genetics
5Signal Transduction–Genetics
6Transforming Growth Factor Beta–Metabolism
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2Armenia, Joshua
3Chatila, Walid K
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39Lazar, Alexander J
40Hammer, Gary D
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100...
atitleOncogenic Signaling Pathways in The Cancer Genome Atlas.
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