Age-related remodelling of oesophageal epithelia by mutated cancer drivers

被引：437

作者：

Yokoyama, Akira ^{[1
,2
]}

Kakiuchi, Nobuyuki ^{[1
,3
]}

Yoshizato, Tetsuichi ^{[1
]}

Nannya, Yasuhito ^{[1
]}

Suzuki, Hiromichi ^{[1
]}

Takeuchi, Yasuhide ^{[1
,4
]}

Shiozawa, Yusuke ^{[1
]}

Sato, Yusuke ^{[1
]}

Aoki, Kosuke ^{[1
]}

Kim, Soo Ki ^{[1
]}

Fujii, Yoichi ^{[1
]}

Yoshida, Kenichi ^{[1
]}

Kataoka, Keisuke ^{[1
]}

Nakagawa, Masahiro M. ^{[1
]}

Inoue, Yoshikage ^{[1
,5
]}

Hirano, Tomonori ^{[1
,3
]}

Shiraishi, Yuichi ^{[6
]}

Chiba, Kenichi ^{[6
]}

Tanaka, Hiroko ^{[7
]}

Sanada, Masashi ^{[8
]}

Nishikawa, Yoshitaka ^{[2
]}

Amanuma, Yusuke ^{[2
]}

Ohashi, Shinya ^{[2
]}

Aoyama, Ikuo ^{[2
]}

Horimatsu, Takahiro ^{[2
]}

Miyamoto, Shin'ichi ^{[3
]}

Tsunoda, Shigeru ^{[5
]}

Sakai, Yoshiharu ^{[5
]}

Narahara, Maiko ^{[9
]}

Brown, J. B. ^{[10
]}

Sato, Yoshitaka ^{[11
]}

Sawada, Genta ^{[12
]}

Mimori, Koshi ^{[12
]}

Minamiguchi, Sachiko ^{[4
]}

Haga, Hironori ^{[4
]}

Seno, Hiroshi ^{[3
]}

Miyano, Satoru ^{[6
,7
]}

Makishima, Hideki ^{[1
]}

Muto, Manabu ^{[2
]}

Ogawa, Seishi ^{[1
,13
]}

机构：

[1] Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan

[2] Kyoto Univ Hosp, Dept Clin Oncol, Kyoto, Japan

[3] Kyoto Univ, Dept Gastroenterol & Hepatol, Kyoto, Japan

[4] Kyoto Univ, Dept Diagnost Pathol, Kyoto, Japan

[5] Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto, Japan

[6] Univ Tokyo, Inst Med Sci, Human Genome Ctr, Lab DNA Informat Anal, Tokyo, Japan

[7] Univ Tokyo, Inst Med Sci, Human Genome Ctr, Lab Sequence Anal, Tokyo, Japan

[8] Nagoya Med Ctr, Dept Adv Diag, Clin Res Ctr, Nagoya, Aichi, Japan

[9] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[10] Kyoto Univ, Life Sci Informat Res Unit, Lab Mol Biosci, Kyoto, Japan

[11] Sato Clin, Okayama, Japan

[12] Kyushu Univ, Dept Surg, Beppu Hosp, Beppu, Oita, Japan

[13] Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, Stockholm, Sweden

来源：

NATURE | 2019年 / 565卷 / 7739期

关键词：

SQUAMOUS-CELL CARCINOMA; GENOMIC CHARACTERIZATION; MUTATIONAL LANDSCAPE; CLONAL HEMATOPOIESIS; ALCOHOL-CONSUMPTION; TUMORIGENESIS; HETEROGENEITY; EVOLUTION; RISK; ACCUMULATION;

D O I：

10.1038/s41586-018-0811-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which-depending on lifestyle risks-may affect cancer development.

引用

页码：312 / +

页数：26

共 43 条

[1] Signatures of mutational processes in human cancer
Alexandrov, Ludmil B.
Nik-Zainal, Serena
Wedge, David C.
Aparicio, Samuel A. J. R.
Behjati, Sam
Biankin, Andrew V.
Bignell, Graham R.
Bolli, Niccolo
Borg, Ake
Borresen-Dale, Anne-Lise
Boyault, Sandrine
Burkhardt, Birgit
Butler, Adam P.
Caldas, Carlos
Davies, Helen R.
Desmedt, Christine
Eils, Roland
Eyfjord, Jorunn Erla
Foekens, John A.
Greaves, Mel
Hosoda, Fumie
Hutter, Barbara
Ilicic, Tomislav
Imbeaud, Sandrine
Imielinsk, Marcin
Jaeger, Natalie
Jones, David T. W.
Jones, David
Knappskog, Stian
Kool, Marcel
Lakhani, Sunil R.
Lopez-Otin, Carlos
Martin, Sancha
Munshi, Nikhil C.
Nakamura, Hiromi
Northcott, Paul A.
Pajic, Marina
Papaemmanuil, Elli
Paradiso, Angelo
Pearson, John V.
Puente, Xose S.
Raine, Keiran
Ramakrishna, Manasa
Richardson, Andrea L.
Richter, Julia
Rosenstiel, Philip
Schlesner, Matthias
Schumacher, Ton N.
Span, Paul N.
Teague, Jon W.
[J]. NATURE, 2013, 500 (7463) : 415 - +
[2] Blokzijl F., PREPRINT
[3] Tissue-specific mutation accumulation in human adult stem cells during life
Blokzijl, Francis
de Ligt, Joep
Jager, Myrthe
Sasselli, Valentina
Roerink, Sophie
Sasaki, Nobuo
Huch, Meritxell
Boymans, Sander
Kuijk, Ewart
Prins, Pjotr
Nijman, Isaac J.
Martincorena, Inigo
Mokry, Michal
Wiegerinck, Caroline L.
Middendorp, Sabine
Sato, Toshiro
Schwank, Gerald
Nieuwenhuis, Edward E. S.
Verstegen, Monique M. A.
van der Laan, Luc J. W.
de Jonge, Jeroen
IJzermans, Jan N. M.
Vries, Robert G.
van de Wetering, Marc
Stratton, Michael R.
Clevers, Hans
Cuppen, Edwin
van Boxtel, Ruben
[J]. NATURE, 2016, 538 (7624) : 260 - +
[4] Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16Ink4a-p19Arf pathway
Bulavin, DV
Phillips, C
Nannenga, B
Timofeev, O
Donehower, LA
Anderson, CW
Appella, E
Fornace, AJ
[J]. NATURE GENETICS, 2004, 36 (04) : 343 - 350
[5] Absolute quantification of somatic DNA alterations in human cancer
Carter, Scott L.
Cibulskis, Kristian
Helman, Elena
McKenna, Aaron
Shen, Hui
Zack, Travis
Laird, Peter W.
Onofrio, Robert C.
Winckler, Wendy
Weir, Barbara A.
Beroukhim, Rameen
Pellman, David
Levine, Douglas A.
Lander, Eric S.
Meyerson, Matthew
Getz, Gad
[J]. NATURE BIOTECHNOLOGY, 2012, 30 (05) : 413 - +
[6] Chai H, 2009, ANN CLIN LAB SCI, V39, P331
[7] Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations
Chang, Jiang
Tan, Wenle
Ling, Zhiqiang
Xi, Ruibin
Shao, Mingming
Chen, Mengjie
Luo, Yingying
Zhao, Yanjie
Liu, Yun
Huang, Xiancong
Xia, Yuchao
Hu, Jinlin
Parker, Joel S.
Marron, David
Cui, Qionghua
Peng, Linna
Chu, Jiahui
Li, Hongmin
Du, Zhongli
Han, Yaling
Tan, Wen
Liu, Zhihua
Zhan, Qimin
Li, Yun
Mao, Weimin
Wu, Chen
Lin, Dongxin
[J]. NATURE COMMUNICATIONS, 2017, 8
[8] Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue
Cooper, Colin S.
Eeles, Rosalind
Wedge, David C.
Van Loo, Peter
Gundem, Gunes
Alexandrov, Ludmil B.
Kremeyer, Barbara
Butler, Adam
Lynch, Andrew G.
Camacho, Niedzica
Massie, Charlie E.
Kay, Jonathan
Luxton, Hayley J.
Edwards, Sandra
Kote-Jarai, Zsofia
Dennis, Nening
Merson, Sue
Leongamornlert, Daniel
Zamora, Jorge
Corbishley, Cathy
Thomas, Sarah
Nik-Zainal, Serena
O'Meara, Sarah
Matthews, Lucy
Clark, Jeremy
Hurst, Rachel
Mithen, Richard
Bristow, Robert G.
Boutros, Paul C.
Fraser, Michael
Cooke, Susanna
Raine, Keiran
Jones, David
Menzies, Andrew
Stebbings, Lucy
Hinton, Jon
Teague, Jon
McLaren, Stuart
Mudie, Laura
Hardy, Claire
Anderson, Elizabeth
Joseph, Olivia
Goody, Victoria
Robinson, Ben
Maddison, Mark
Gamble, Stephen
Greenman, Christopher
Berney, Dan
Hazell, Steven
Livni, Naomi
[J]. NATURE GENETICS, 2015, 47 (04) : 367 - U118
[9] Epidermal Notch1 Loss Promotes Skin Tumorigenesis by Impacting the Stromal Microenvironment
Demehri, Shadmehr
Turkoz, Ahu
Kopan, Raphael
[J]. CANCER CELL, 2009, 16 (01) : 55 - 66
[10] Medical progress - Esophageal cancer
Enzinger, PC
Mayer, RJ
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (23) : 2241 - 2252

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