41 research outputs found
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
- Author
- Abeshouse A
- Adebamowo C
- Adebamowo SN
- Akbani R
- Akbani R
- Akeredolu T
- Ally A
- Anderson ML
- Anderson ML
- Anur P
- Anur P
- Appelbaum EL
- Armenia J
- Auman JT
- Auman JT
- Bailey MH
- Bailey MH
- Bailey MH
- Baker L
- Balasundaram M
- Balu S
- Barthel FP
- Bartlett J
- Baylin SB
- Behera M
- Belyaev D
- Bennett J
- Benz C
- Benz C
- Beroukhim R
- Birrer M
- Bocklage T
- Bodenheimer T
- Boice L
- Bootwalla MS
- Bowen J
- Bowen J
- Bowlby R
- Bowlby R
- Boyd J
- Brohl AS
- Brohl AS
- Brooks D
- Byers L
- Byers L
- Carlsen R
- Castro P
- Chen H-W
- Cherniack AD
- Cherniack AD
- Cherniack AD
- Chibon F
- Chin L
- Cho J
- Chuah E
- Chudamani S
- Cibulskis C
- Cooper LAD
- Cooper LAD
- Cooper LAD
- Cope L
- Cope L
- Cope L
- Cordes MG
- Crain D
- Curley E
- Danilova L
- Danilova L
- Dao F
- Davis IJ
- Davis IJ
- Davis LE
- Davis LE
- de Rijn MV
- Defreitas T
- Delman K
- Demchok JA
- Demetri GD
- Demetri GD
- Demetri GD
- Demetri GD
- Demicco EG
- Demicco EG
- Dhalla N
- Diao L
- Ding L
- DiSaia P
- Dottino P
- Doyle LA
- Doyle LA
- Drill E
- Drill E
- Dubina M
- Eschbacher J
- Fedosenko K
- Felau I
- Ferguson ML
- Frazer S
- Fronick CC
- Fulidou V
- Fulton LA
- Fulton RS
- Gabriel SB
- Gao J
- Gao Q
- Gardner J
- Gastier-Foster JM
- Gay CM
- Gay CM
- Gehlenborg N
- Gerken M
- Getz G
- Godwin AK
- Godwin AK
- Godwin AK
- Godwin EM
- Gordienko E
- Grilley-Olsen JE
- Grilley-Olson JE
- Grilley-Olson JE
- Grilley-Olson JE
- Gutman DA
- Gutman DA
- Gutmann DH
- Gutmann DH
- Hayes DN
- Hayes DN
- Hegde AM
- Hegde AM
- Heiman DI
- Heins Z
- Helsel C
- Hepperla AJ
- Hepperla AJ
- Higgins K
- Hoadley KA
- Hoadley KA
- Hobensack S
- Holt RA
- Hoon DB
- Hoon DB
- Hornick JL
- Hornick JL
- Hoyle AP
- Hu X
- Huang M
- Hutter CM
- Iacocca M
- Ingram DR
- Ittmann M
- Iype L
- Iype L
- Iype L
- Jefferys SR
- Jones CD
- Jones KB
- Jones SJM
- Kalir T
- Karlan BY
- Karseladze A
- Kasaian K
- Kasaian K
- Kim J
- Kim J
- Kundra R
- Kuo H
- Ladanyi M
- Ladanyi M
- Lai PH
- Laird PW
- Larsson E
- Lawrence MS
- Lazar AJ
- Lazar AJ
- Lazar AJ
- Lazar AJ
- Lazar AJ
- Lazar AJ
- Lazar AJ
- Lee D
- Lee S
- Lee S
- Lehmann K-V
- Leraas KM
- Leraas KM
- Lester J
- Levine DA
- Li I
- Lichtenberg TM
- Lichtenberg TM
- Lichtenberg TM
- Lin P
- Liu EM
- Liu J
- Liu W
- Lolla L
- Lu Y
- Ma Y
- Madan R
- Maglinte DT
- Magliocco A
- Maki RG
- Maki RG
- Mallery D
- Manikhas G
- Mardis ER
- Mariamidze A
- Marra MA
- Martignetti JA
- Martinez C
- Mayo M
- McLellan MD
- McLellan MD
- Meier S
- Meng S
- Meyerson M
- Mieczkowski PA
- Miller CA
- Miller CA
- Mills GB
- Moore RA
- Morris S
- Mose LE
- Mozgovoy E
- Mungall AJ
- Mungall K
- Mungall K
- Nalisnik M
- Nalisnik M
- Naresh R
- Newton Y
- Noble MS
- Noble MS
- Novak JE
- Ochoa A
- Olvera N
- Owonikoko TK
- Paklina O
- Parfitt J
- Parker JS
- Parker JS
- Pastore A
- Paulauskis J
- Penny R
- Pereira E
- Perou AH
- Perou CM
- Pihl T
- Pollock RE
- Potapova O
- Radenbaugh AJ
- Ramalingam SS
- Ramirez N
- Ramirez NC
- Rathmell WK
- Raut CP
- Raut CP
- Raut CP
- Raut CP
- Reilly C
- Reynolds SM
- Riedel RF
- Riedel RF
- Riedel RF
- Roach J
- Robertson AG
- Robertson AG
- Robertson AG
- Roszik J
- Roszik J
- Rubin BP
- Rubin BP
- Sadeghi S
- Sadeghi S
- Saksena G
- Salner A
- Sanchez-Vega F
- Sanchez-Vega F
- Sanchez-Vega F
- Sanchez-Vega F
- Sander C
- Schein JE
- Schmidt HK
- Schultz N
- Schultz N
- Schumacher SE
- Sekhon H
- Senbabaoglu Y
- Setdikova G
- Shelton C
- Shelton T
- Shen R
- Shen R
- Shi Y
- Shih J
- Shih J
- Shih J
- Shmulevich I
- Sica GL
- Simons JV
- Singer S
- Singer S
- Sipahimalani P
- Skelly T
- Socci N
- Sofia HJ
- Soloway MG
- Spellman P
- Sun Q
- Swanson P
- Tam A
- Tan D
- Tarnuzzer R
- Thiessen N
- Thompson E
- Thorne LB
- Tong P
- Torres KE
- Torres KE
- Van Den Berg DJ
- Van Tine BA
- Veluvolu U
- Verhaak R
- Voet D
- Voronina O
- Wan Y
- Wang J
- Wang Z
- Weinstein JN
- Weinstein JN
- Weisenberger DJ
- Wilkerson MD
- Wilson RK
- Wise L
- Wong T
- Wong W
- Wong W
- Wong W
- Wrangle J
- Wu Y
- Wyczalkowski M
- Yang L
- Yau C
- Yau C
- Yellapantula V
- Zenklusen JC
- Zenklusen JC
- Zhang H
- Zhang H
- Zhang JJ
- Zmuda E
- Publication venue
- CELL PRESS
- Publication date
- 02/11/2017
- Field of study
Summary
Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types
Recommended from our members
Comprehensive molecular characterization of gastric adenocarcinoma
- Author
- Abdel-Misih Raafat
- Ajani Jaffer
- Akbani Rehan
- Albert Monique
- Alexopoulou Iakovina
- Ally Adrian
- Alonso Shelley
- Askoy B. Arman
- Ayala Brenda
- Balasundaram Miruna
- Bartlett John
- Bass Adam J.
- Baylin Stephen B.
- Beer David G.
- Belyaev Smitry
- Bennett Joseph
- Benz Christopher
- Bernard Brady
- Beroukhim Rameen
- Birol Inanc
- Black Aaron D.
- Bootwalla Moiz S.
- Boussioutas Alex
- Bowen Jay
- Bowlby Reanne
- Bristow Christopher A.
- Brooks Denise
- Brown Jennifer
- Brzezinski Jakub
- Burton Robert
- Butterfield Yaron S. N.
- Camargo M. Constanza
- Carlsen Rebecca
- Carney Julie Ann
- Carter Scott L.
- Cheong Jae-Ho
- Cherniack Andrew
- Cherniack Andrew D.
- Chin Lynda
- Cho Eunjung
- Cho Juok
- Chu Andy
- Chu Justin
- Chuah Eric
- Chudamani Sudha
- Chun Hye-Jung E.
- Cibulskis Kristian
- Ciriello Giovanni
- Clarke Amanda
- Crain Daniel
- Curely Erin
- Curley Erin
- Curtis Christina
- Davidsen Tanja
- Demchok John A.
- Dhalla Noreen
- Dhir Rajiv
- DiCara Daniel
- Ding Li
- Dolzhansky Oleg
- Dresdner Gideon
- Eley Greg
- Engel Jay
- Fedosenko Konstantin
- Fisher Sheila
- Frazer Scott
- Gabriel Stacey B.
- Gao Jianjiong
- Gardner Johanna
- Garman Katherine
- Gastier-Foster Julie M.
- Gehlenborg Nils
- Getz Gad
- Gross Benjamin
- Guin Ranabir
- Gulley Margaret
- Hadjipanayis Angela
- Haussler David
- Heiman David I.
- Helsel Carmen
- Herman James G.
- Hinoue Toshinori
- Holt Robert A.
- Hutter Carolyn M.
- Iacocca Mary
- Ibbs Matthew
- Iype Lisa
- Jacobsen Anders
- Janjigian Yelena Y.
- Jensen Mark A.
- Jones Steven J.M.
- Jung Joonil
- Kasaian Katayoon
- Kelsen David P.
- Kemkes Ariane
- Kim Hark K.
- Kim Jaegil
- Kim Jihun
- Kim Sang-Bae
- Korski Konstanty
- Kramer Roger W.
- Kreisberg Richard
- Kucherlapati Raju
- Kwon Sun-Young
- Kycler Witold
- Ladanyi Marc
- Lai Phillip H.
- Laird Peter W.
- Lander Eric S.
- Landreneau Rodney
- Lau Kevin
- Lawrence Michael S.
- Lee Darlene
- Lee Jae-Hyuk
- Lee Ju-Seog
- Lee Semin
- Lee William
- Leiserson Mark D. M.
- Leporowska Ewa
- Leraas Kristen M.
- Li Haiyan A.
- Lichtenberg Tara M.
- Lichtenstein Lee
- Lim Emilia
- Lin Pei
- Ling Shiyun
- Liu Jia
- Liu Wenbin
- Liu Yingchun
- Lu Yiling
- Luketich James
- Ma Yussanne
- Mackiewicz Andrzej
- Mahadeshwar Harshad S.
- Mallery David
- Manikhas Georgy
- Marra Marco A.
- Mayo Michael
- McAllister Cynthia
- McCall Shannon J.
- McLellan Michael
- Meyerson Matthew
- Miller Michael
- Mills Shaw Kenna R.
- Mills Gordon
- Mills Gordon B.
- Moore Richard A.
- Morris Scott
- Mungall Andrew J.
- Mungall Karen L.
- Murawa Dawid
- Murawa Pawel
- Murray Bradley A.
- Ng Sam
- Ng Santa Cruz Sam
- Nip Ka Ming
- Niu Beifang
- Noble Michael S.
- Odze Robert
- Ojesina Akinyemi I.
- Pantazi Angeliki
- Parfenov Michael
- Park Do-Youn
- Park Peter J.
- Park Young S.
- Paulauskis Joseph
- Pedamallu Chandra
- Pedamallu Chandra Sekhar
- Pennathur Arjun
- Penny Robert
- Piazuelo M. Blanca
- Pihl Todd
- Potapova Olga
- Protopopov Alexei
- Rabeno Brenda
- Rabkin Charles S.
- Raman Rohini
- Ramirez Nilsa C.
- Ramirez Ricardo
- Rao Arvind
- Raphael Benjamin J.
- Rathmell W. Kimryn
- Ren Xiaojia
- Reynolds Sheila M.
- Robertson A. Gordon
- Rosenberg Mara
- Rovira Hector
- Sakai Ryo
- Saksena Gordon
- Sander Chris
- Santoso Netty
- Schein Jacqueline E.
- Schneider Barbara G.
- Schultz Nikolaus
- Schumacher Steven E.
- Seidman Jonathan
- Senbabaoglu Yasin
- Seth Sahil
- Shelton Candace
- Shelton Troy
- Shen Hui
- Shen Ronglai
- Sherman Mark
- Sheth Margi
- Shmulevich Ilya
- Sinha Rileen
- Sipahimalani Payal
- Sofia Heidi J.
- Song Xingzhi
- Sougnez Carrie
- Spychała Arkadiusz
- Stojanov Petar
- Stuart Josh M.
- Suchorska Wiktoria M.
- Sumer S. Onur
- Sun Yichao
- Tabak Barbara
- Tabler Teresa R.
- Tam Angela
- Tang Jiabin
- Tang Laura
- Tarnuzzer Roy
- Tasman Natalie
- Tatka Honorata
- Taylor Barry S.
- Taylor-Weiner Amaro
- Teresiak Marek
- Thiessen Nina
- Thorsson Vesteinn
- Thorsson Vésteinn
- Triche Timothy
- Van Den Berg David J.
- Verhaak Roeland G.W.
- Voet Doug
- Voronina Olga
- Walton Jessica
- Wan Yunhu
- Wang Zhining
- Weaver Stephanie
- Weinhold Nils
- Weinstein John N.
- Weisenberger Daniel J.
- Willis Joseph E.
- Wise Lisa
- Wiznerowicz Maciej
- Wu Hsin-Ta
- Xi Ruibin
- Xu Andrew W.
- Yang Da
- Yang Liming
- Yang Lixing
- Zack Travis I.
- Zenklusen Jean Claude
- Zhang Hailei
- Zhang Jianhua
- Zhang Wei
- Zmuda Erik
- Zou Lihua
- ŁaŸniak Radoslaw
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/10/2014
- Field of study
Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies
Pan-cancer analysis of whole genomes
- Author
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- Short C. f
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- Tatsuno
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- Thayer
- The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium View Correspondence (jump link)
- Thiessen
- Thomas
- Thomas
- Thompson
- Thompson
- Thompson
- Thorne
- Thorne
- Thorogood
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- tj Sweep
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- vo Taniguchi
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- Weinberger
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- Wiznerowicz
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- X. oi
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- Y. gl
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- Y. hq
- Y. ia
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- Y. rg
- Y. rj
- Y. rm
- Y. S. jf
- Y. uz
- Y. vr
- Y. wt
- Y. yc
- ya Al-Ahmadie
- Yachida
- Yamaguchi
- Yamaguchi T. N. k
- Yamamoto
- Yamaue
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- Yang
- Yang
- Yang
- Yang
- Yao
- Yaspo
- Yates
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- Yellapantula
- Yellapantula
- yh Bathe
- yj Baylin
- Yoon
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- Yu
- Yu
- Yuan
- Yugawa
- z ah
- Z. ej
- Z. ep
- Z. fr
- Z. hv
- Z. hy
- Z. jq
- Z. kt
- Z. oe
- Zaikova
- Zapatka
- zd Gershenwald
- Zenklusen
- Zeps
- zf Ghossein
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang H. b
- Zhao
- Zheng
- Zhou
- Zhou
- Zhu
- Zhu
- zi zj
- zm Jayaseelan
- Zou
- Zou
- zt Kim
- zw Lewis
- Ó. A. th
- Ø. sk
- Publication venue
- Publication date
- 11/12/2019
- Field of study
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
- Author
- Abeshouse Adam
- Adebamowo Clement
- Adebamowo Sally N.
- Akbani Rehan
- Akeredolu Teniola
- Ally Adrian
- Anderson Matthew L.
- Anur Pavana
- Appelbaum Elizabeth L.
- Armenia Joshua
- Auman J. Todd
- Bailey Matthew H.
- Baker Laurence
- Balasundaram Miruna
- Balu Saianand
- Barthel Floris P.
- Bartlett John
- Baylin Stephen B.
- Behera Madhusmita
- Belyaev Dmitry
- Bennett Joesph
- Benz Christopher
- Beroukhim Rameen
- Birrer Michael
- Bocklage Thèrése
- Bodenheimer Tom
- Boice Lori
- Bootwalla Moiz S.
- Bowen Jay
- Bowlby Reanne
- Boyd Jeff
- Brohl Andrew S.
- Brooks Denise
- Byers Lauren
- Carlsen Rebecca
- Castro Patricia
- Chen Hsiao-Wei
- Cherniack Andrew D.
- Chibon Fréderic
- Chin Lynda
- Cho Juok
- Chuah Eric
- Chudamani Sudha
- Cibulskis Carrie
- Cooper Lee A.D.
- Cope Leslie
- Cordes Matthew G.
- Crain Daniel
- Curley Erin
- Danilova Ludmila
- Dao Fanny
- Davis Ian J.
- Davis Lara E.
- Defreitas Timothy
- Delman Keith
- Demchok John A.
- Demetri George D.
- Demicco Elizabeth G.
- Dhalla Noreen
- Diao Lixia
- Ding Li
- DiSaia Phil
- Dottino Peter
- Doyle Leona A.
- Drill Esther
- Dubina Michael
- Eschbacher Jennifer
- Fedosenko Konstantin
- Felau Ina
- Ferguson Martin L.
- Frazer Scott
- Fronick Catrina C.
- Fulidou Victoria
- Fulton Lucinda A.
- Fulton Robert S.
- Gabriel Stacey B.
- Gao Jianjiong
- Gao Qingsong
- Gardner Johanna
- Gastier-Foster Julie M.
- Gay Carl M.
- Gehlenborg Nils
- Gerken Mark
- Getz Gad
- Godwin Andrew K.
- Godwin Eryn M.
- Gordienko Elena
- Grilley-Olson Juneko E.
- Gutman David A.
- Gutmann David H.
- Hayes D. Neil
- Hegde Apurva M.
- Heiman David I.
- Heins Zachary
- Helsel Carmen
- Hepperla Austin J.
- Higgins Kelly
- Hoadley Katherine A.
- Hobensack Shital
- Holt Robert A.
- Hoon Dave B.
- Hornick Jason L.
- Hoyle Alan P.
- Hu Xin
- Huang Mei
- Hutter Carolyn M.
- Iacocca Mary
- Ingram Davis R.
- Ittmann Michael
- Iype Lisa
- Jefferys Stuart R.
- Jones Corbin D.
- Jones Kevin B.
- Jones Steven J.M.
- Kalir Tamara
- Karlan Beth Y.
- Karseladze Apollon
- Kasaian Katayoon
- Kim Jaegil
- Kundra Ritika
- Kuo Hanluen
- Ladanyi Marc
- Lai Phillip H.
- Laird Peter W.
- Larsson Erik
- Lawrence Michael S.
- Lazar Alexander J.
- Lee Darlene
- Lee Sanghoon
- Lehmann Kjong-Van
- Leraas Kristen M.
- Lester Jenny
- Levine Douglas A.
- Li Irene
- Lichtenberg Tara M.
- Lin Pei
- Liu Eric Minwei
- Liu Jia
- Liu Wenbin
- Lolla Laxmi
- Lu Yiling
- Ma Yussanne
- Madan Rashna
- Maglinte Dennis T.
- Magliocco Anthony
- Maki Robert G.
- Mallery David
- Manikhas Georgy
- Mardis Elaine R.
- Mariamidze Armaz
- Marra Marco A.
- Martignetti John A.
- Martinez Cathleen
- Mayo Michael
- McLellan Michael D.
- Meier Sam
- Meng Shaowu
- Meyerson Matthew
- Mieczkowski Piotr A.
- Miller Christopher A.
- Mills Gordon B.
- Moore Richard A.
- Morris Scott
- Mose Lisle E.
- Mozgovoy Evgeny
- Mungall Andrew J.
- Mungall Karen
- Nalisnik Michael
- Naresh Rashi
- Newton Yulia
- Noble Michael S.
- Novak Janet E.
- Ochoa Angelica
- Olvera Narciso
- Owonikoko Taofeek K.
- Paklina Oxana
- Parfitt Jeremy
- Parker Joel S.
- Pastore Alessandro
- Paulauskis Joseph
- Penny Robert
- Pereira Elena
- Perou Amy H.
- Perou Charles M.
- Pihl Todd
- Pollock Raphael E.
- Potapova Olga
- Radenbaugh Amie J.
- Ramalingam Suresh S.
- Ramirez Nilsa C.
- Rathmell W. Kimryn
- Raut Chandrajit P.
- Reilly Colleen
- Reynolds Sheila M.
- Riedel Richard F.
- Roach Jeffrey
- Robertson A. Gordon
- Roszik Jason
- Rubin Brian P.
- Sadeghi Sara
- Saksena Gordon
- Salner Andrew
- Sanchez-Vega Francisco
- Sander Chris
- Schein Jacqueline E.
- Schmidt Heather K.
- Schultz Nikolaus
- Schumacher Steven E.
- Sekhon Harman
- Senbabaoglu Yasin
- Setdikova Galiya
- Shelton Candace
- Shelton Troy
- Shen Ronglai
- Shi Yan
- Shih Juliann
- Shmulevich Ilya
- Sica Gabriel L.
- Simons Janae V.
- Singer Samuel
- Sipahimalani Payal
- Skelly Tara
- Socci Nicholas
- Sofia Heidi J.
- Soloway Matthew G.
- Spellman Paul
- Sun Qiang
- Swanson Patricia
- Tam Angela
- Tan Donghui
- Tarnuzzer Roy
- Thiessen Nina
- Thompson Eric
- Thorne Leigh B.
- Tong Pan
- Torres Keila E.
- van de Rijn Matt
- Van Den Berg David J.
- Van Tine Brian A.
- Veluvolu Umadevi
- Verhaak Roel
- Voet Doug
- Voronina Olga
- Wan Yunhu
- Wang Jing
- Wang Zhining
- Weinstein John N.
- Weisenberger Daniel J.
- Wilkerson Matthew D.
- Wilson Richard K.
- Wise Lisa
- Wong Tina
- Wong Winghing
- Wrangle John
- Wu Ye
- Wyczalkowski Matthew
- Yang Liming
- Yau Christina
- Yellapantula Venkata
- Zenklusen Jean C.
- Zhang Hailei
- Zhang Hongxin
- Zhang Jiashan (Julia)
- Zmuda Erik
- Publication venue
- Publication date
- 01/01/2017
- Field of study
Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types
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- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 02/03/2020
- Field of study
Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- Author
- A Gordon Robertson
- Abdullah Kahraman
- Abel Gonzalez-Perez
- Adam A Margolin
- Adam Abeshouse
- Adam Grundhoff
- Adam J Struck
- Adam J Struck
- Adam J Wright
- Adam Lambert
- Adam P Butler
- Adam P Butler
- Adel El-Naggar
- Adnan M Nagrial
- Adrian Ally
- Adrian Baez-Ortega
- Adrian Thorogood
- Adriana Salcedo
- Adrienne M Flanagan
- Ake Borg
- Akihiro Fujimoto
- Akihiro Suzuki
- Akinyemi I Ojesina
- Alain Viari
- Alan J Robertson
- Alan P Hoyle
- Alan Thompson
- Alasdair Stenhouse
- Alastair M Thompson
- Aldo Scarpa
- Alessandro Pastore
- Alex Buchanan
- Alex Buchanan
- Alexander Claviez
- Alexander J Lazar
- Alexander Martinez-Fundichely
- Alfonso Muñoz
- Alfonso Valencia
- Aliaksei Z Holik
- Alice Meng
- Alicia L Bruzos
- Allison Creason
- Allison P Heath
- Alvin Wei Tian Ng
- Alvis Brazma
- Amaro Taylor-Weiner
- Amber L Johns
- Amie Radenbaugh
- Amit G Deshwar
- Ana Dueso-Barroso
- Ana Mijalkovic Mijalkovic-Lazic
- Ana Milovanovic
- Ana Milovanovic
- Andre Kahles
- Andrea Haake
- Andrea Holbrook
- Andrea L Richardson
- Andrea Mafficini
- Andrea Ruzzenente
- Andreas Behren
- Andreas Rosenwald
- Andreia V Pinho
- Andrew Berchuck
- Andrew D Cherniack
- Andrew J Dunford
- Andrew J Mungall
- Andrew J Spillane
- Andrew Menzies
- Andrew Menzies
- Andrew P Barbour
- Andrew Tutt
- Andrew V Biankin
- Andrey Korshunov
- Andrés Lanzós
- Andy Cafferkey
- Andy G Lynch
- Angela Chou
- Angela N Brooks
- Angela Tam
- Angelica Ochoa
- Angelika N Christ
- Angelo P Dei Tos
- Anieta M Sieuwerts
- Anil K Sood
- Anita Langerød
- Anja Füllgrabe
- Anke K Bergmann
- Ann-Marie Patch
- Anna deFazio
- Anna Ehinger
- Anna Fitzgerald
- Anne Hamilton
- Anne Vincent-Salomon
- Anne Y Warren
- Anne-Lise Børresen-Dale
- Annegien Broeks
- Anthony DiBiase
- Anthony J Gill
- Anthony Ng
- Anthony R Green
- Antonia L Pritchard
- Antonio Pea
- Antonios Koures
- Aparna Prasad
- Apurva M Hegde
- Aquila Fatima
- Arcadi Navarro
- Arie B Brinkman
- Arif O Harmanci
- Arindam Maitra
- Armando Lopez-Guillermo
- Arndt Borkhardt
- Arnoud Boot
- Asger Hobolth
- Ashley Williams
- Ashton A Connor
- Atul J Butte
- Aurélien Chateigner
- Austin J Hepperla
- Axel Aretz
- Aya Sasaki-Oku
- Ayellet V Segre
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- Bernice H Wong
- Beth Karlan
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- Stephan Wolf
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- Stuart Edmonds
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- Subhajit Sengupta
- Sue Merson
- Suet-Feung Chin
- Sultan T Al-Sedairy
- Sung-Min Ahn
- Sung-Soo Yoon
- Sunghoon Cho
- Sunil R Lakhani
- Suresh Ramalingam
- Susan Bullman
- Susanna L Cooke
- Sushant Kumar
- Sushant Kumar
- Suyash S Shringarpure
- Syed Haider
- Sylvia Asa
- Søren Brunak
- Takafumi N Yamaguchi
- Takafumi N Yamaguchi
- Takanori Hasegawa
- Takashi Yugawa
- Takashi Yugawa
- Takuji Okusaka
- Tal Shmaya
- Tannistha Nandi
- Taobo Hu
- Taobo Hu
- Tapio Visakorpi
- Tara J Skelly
- Tari A King
- Tatsuhiko Tsunoda
- Tatsuhiro Shibata
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- Tetsuo Ushiku
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- Thorsten Zenz
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- Tim Ley
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- Tina Wong
- Tirso Pons
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- Tobias Rausch
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- Tom Mikkelsen
- Tom Roques
- Tomas J Tanskanen
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- Tomoko Urushidate
- Torill Sauer
- Toru Nakamura
- Treasa A McPherson
- Troy Shelton
- Tsun-Po Yang
- Ultan McDermott
- Umadevi Veluvolu
- Umut H Toprak
- Valerie Jakrot
- Varsha Tembe
- Vasilisa A Rudneva
- Venkata D Yellapantula
- Venkata D Yellapantula
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- Veronica Y Sabelnykova
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- Vincenzo Corbo
- Vishal S Chandan
- Volker Hovestadt
- W Kimryn Rathmell
- W M Linehan
- Walker Hale
- Wan Choi
- Wanding Zhou
- Wang Liang-Bo
- Weerasinghe Amila
- Wei Jiao
- Wendl Michael C
- Wenyi Wang
- Wenyi Wang
- Wenyi Wang
- Wheeler David A
- William B Isaacs
- William C Faquin
- William Friedman
- William Howat
- William U Meyerson
- Willie Yu
- Winghing Wong
- Wojciech Bazant
- Wolfgang Huber
- Wolfram Klapper
- Xavier Estivill
- Xavier Pivot
- Xiao Xiao
- Xiaobo Li
- Xiaoping Su
- Xiaotong Li
- Xiaotong Yao
- Xing Hua
- Xingmin Liu
- Xinyue Li
- Xiuqing Zhang
- Xiuqing Zheng
- Xose S Puente
- Xuan Le
- Xuanping Zhang
- Xuemei Luo
- Xueqing Zou
- Yan Shi
- Yan Zhang
- Yang Wu
- Yang Yang
- Yann Joly
- Yanxun Xu
- Yao He
- Yasin Senbabaoglu
- Yassen Assenov
- Yasser Riazalhosseini
- Yasuhito Arai
- Yasushi Rino
- Yasushi Totoki
- Yeng Ang
- Yi Huang
- Yi Huang
- Yifei Men
- Yiling Lu
- Yilong Li
- Yingyan Yu
- Yiwen Chen
- Yogesh Kumar
- Yogesh Kumar
- Yoke-Eng Chiew
- Yong Hou
- Yong Zhou
- Yong-Jie Lu
- Yongzhan Nie
- Yosef E Maruvka
- Yosef E Maruvka
- Yoshiiku Kawakami
- Young Seok Ju
- Youngchoon Woo
- Youngil Koh
- Youngwook Kim
- Youyong Lu
- Yu Fan
- Yu Fan
- Yu Fan
- Yu-Jia Shiah
- Yuan Ji
- Yuan Yuan
- Yuichi Shiraishi
- Yulia Newton
- Yulia Rubanova
- Yumeng Wang
- Yupeng Cun
- Yussanne Ma
- Zachary Heins
- Zechen Chong
- Zechen Chong
- Zemin Zhang
- Zhaohong Chen
- Zhenggang Wu
- Zhenggang Wu
- Zhining Wang
- Zhongming Zhao
- Ziao Lin
- Zsofia Kote-Jarai
- Ólafur Andri Stefánsson
- Øystein Garred
- Publication venue
- Nature Communications
- Publication date
- 01/01/2020
- Field of study
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
- Author
- Abassi Yama
- Abelin Jennifer G
- Abolhalaj Milad
- Abraham Tara S
- Adam Ammar
- Adams David
- Adams Homer
- Adams Sarah F
- Adamus Tomasz
- Addepalli Murali
- Addepalli Murali
- Adjei Alex A
- Agapova Larissa
- Agarwala Sanjiv
- Ager Casey
- Aggarwal Charu
- Agnello Giulia
- Agudo Judith
- Aguilar Ethan G
- Aguilera Todd
- Ahamadi Malidi
- Ahn Yong-Oon
- Ahrens Eric T
- Aizer Ayal
- Ajina Reham
- Akerley Wallace
- Al-Muftah Mariam
- Albershardt Tina C
- Albershardt Tina C
- Albrekt Ann-Sofie
- Alekar Shilpa
- Alemany Ramon
- Alemany Ramon
- Alexander Brian
- Allbritton Omaira
- Allen Clint T
- Alley Evan W
- Allison James
- Allison James
- Allison James
- Alston Tesha
- Alt Jürgen
- Alters Susan
- Amatulli Michael
- Anand Snjezana
- Anand Snjezana
- Anand Snjezana
- Anderson Clark
- Anderson Mark
- Andersson Bengt
- Andre Pascale
- Andtbacka Robert H I
- Andtbacka Robert H I
- Angiuoli Sam
- Ansari Tameem
- Anthony Scott
- Antonarakis Emmanuel S
- Antonia Scott J
- Anwar Firoz
- Aquino-Michaels Keston
- Archer Jacob F
- Arina Ainhoa
- Armand Philippe
- Armenta Paul
- Armet Caroline M
- Arnoux Thomas
- Ascarateil Stephane
- Askmyr David
- Atkins Michael
- Atkins Michael B
- Atkinson Victoria
- Au Katrina
- Autio Karen A
- Awad Mark
- Bagarazzi Mark
- Bai Dina
- Baia Gilson
- Baird Jason
- Bajaj Anshika
- Balatoni Timea
- Balboni Tracy
- Balch Leslie
- Bang Andrew
- Bao Riyue
- Bao Yangyi
- Bao Yangyi
- Barakat David
- Barberi Theresa
- Barker Christopher A
- Barnea Eytan
- Barras David
- Bartkowiak Todd
- Bartlett David
- Bartlett David
- Bartlett David
- Bartlett David
- Barton Sunjay M
- Barve Minal
- Bauer Todd
- Bauer Todd W
- Bauman Julie
- Baumgaertner Petra
- Bauml Joshua
- Beceren-Braun Figen
- Beck Kristen
- Becker Annette
- Beckers Johannes
- Beckett Michael A
- Bedognetti Davide
- Bedognetti Davide
- Bedognetti Davide
- Bell Bryan
- Bell Charles J M
- Bell Peter
- Beltran Pedro
- Bender Lewis H
- Bender Steven
- Bennett Mark K
- Benz Steven
- Bera Tapan
- Berglund Peter
- Berglund Peter
- Berkey Sara
- Bernatchez Chantale
- Berry John S
- Berzofsky Jay A
- Bhardwaj Nina
- Bian Zhen
- Bianco Alberto
- Biediger Ronald J
- Bifulco Carlo
- Bigley Alison
- Bingham Patrick
- Biniszkiewicz Detlev M
- Bischoff Helge
- Blake Zoe
- Blake Zoe
- Blakely Collin
- Blazar Bruce R
- Blogowski Wojciech
- Bloom Anja C
- Boehm Jesse
- Bokovanov Vladimir
- Bommareddy Praveen K
- Bommareddy Praveen K
- Bommareddy Praveen K
- Bommareddy Praveen K
- Booth Jamie
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- Shabanowitz Jeffrey
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- Shafren Darren
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- Shamalov Katerina
- Shanker Anil
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- Sharma Manish
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- Sharma Padmanee
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- Ujhelyi Mihaly
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- Unfricht Darryn
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- Urban Julie
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- Valsesia-Wittmann Sandrine
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- Van der Meijs Pien
- van Vugt Marianne
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- Xu Chunxiao
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- Yagiz Kader
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- Yan Jian
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- Ylösmäki Erkko
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- Zafar Sadia
- Zalevsky Jonathan
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- Zalevsky Jonathan
- Zalevsky Jonathan
- Zappasodi Roberta
- Zappasodi Roberta
- Zauderer Maurice
- Zeh Herbert
- Zelenetz Andrew D
- Zeng Weiping
- Zeng Xue
- Zha Yuanyuan
- Zhang Danhui
- Zhang Jing
- Zhang Ping
- Zhang Qifang
- Zhang Shannon S
- Zhang Theresa
- Zhang Winter
- Zhang Yanping
- Zhao Fei
- Zhao Leyna
- Zhao Xingli
- Zheng Lianxing
- Zheng Wenxin
- Zheng Xianxian
- Zheng Yi
- Zhong Hong
- Zhou Li
- Zhou Xiangjun
- Zippelius Alfred
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zou Jun
- Zuba-Surma Ewa
- Zubkova Olga
- Zureikat Amer
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2016
- Field of study
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Recognizing the Continuous Nature of Expression Heterogeneity and Clinical Outcomes in Clear Cell Renal Cell Carcinoma
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
CTLA-4 blockade drives loss of T<sub>reg</sub> stability in glycolysis-low tumours.
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/03/2021
- Field of study
Limiting metabolic competition in the tumour microenvironment may increase the effectiveness of immunotherapy. Owing to its crucial role in the glucose metabolism of activated T cells, CD28 signalling has been proposed as a metabolic biosensor of T cells <sup>1</sup> . By contrast, the engagement of CTLA-4 has been shown to downregulate T cell glycolysis <sup>1</sup> . Here we investigate the effect of CTLA-4 blockade on the metabolic fitness of intra-tumour T cells in relation to the glycolytic capacity of tumour cells. We found that CTLA-4 blockade promotes metabolic fitness and the infiltration of immune cells, especially in glycolysis-low tumours. Accordingly, treatment with anti-CTLA-4 antibodies improved the therapeutic outcomes of mice bearing glycolysis-defective tumours. Notably, tumour-specific CD8 <sup>+</sup> T cell responses correlated with phenotypic and functional destabilization of tumour-infiltrating regulatory T (T <sub>reg</sub> ) cells towards IFNγ- and TNF-producing cells in glycolysis-defective tumours. By mimicking the highly and poorly glycolytic tumour microenvironments in vitro, we show that the effect of CTLA-4 blockade on the destabilization of T <sub>reg</sub> cells is dependent on T <sub>reg</sub> cell glycolysis and CD28 signalling. These findings indicate that decreasing tumour competition for glucose may facilitate the therapeutic activity of CTLA-4 blockade, thus supporting its combination with inhibitors of tumour glycolysis. Moreover, these results reveal a mechanism by which anti-CTLA-4 treatment interferes with T <sub>reg</sub> cell function in the presence of glucose
Putative biomarkers for predicting tumor sample purity based on gene expression data
- Author
- A Ribas
- Adrienna Bingham
- B Li
- C Wu
- C Zheng
- D Aran
- D Opitz
- David M. Umbach
- DF Quail
- DH Wolpert
- EA Houseman
- G Bindea
- H Hackl
- J Elith
- JH Friedman
- JN Weinstein
- K Yoshihara
- KA Hoadley
- L Breiman
- L Breiman
- Leping Li
- M Galar
- M Karaayvaz
- M. Galar
- Michael D. Iglesia
- N Altman
- NQ Zhang
- Qi-Jing Li
- R Polikar
- RE Schapire
- RE Schapire
- SJ Turley
- SL Carter
- SV Puram
- X Zheng
- X Zheng
- Y Ganjisaffar
- Y Li
- Y Li
- Y Senbabaoglu
- Yuan Zhuang
- Yuanyuan Li
- Z Luo
- Z Wang
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study