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Semantic Scholar Open Access 2017 918 sitasi

The evolutionary history of 2,658 cancers

M. Gerstung Clemency Jolly I. Leshchiner S. Dentro Santiago Gonzalez +65 lainnya
Lihat Sumber DOI

Abstrak

Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers 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)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection. Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Topik & Kata Kunci

Medicine Biology Computer Science

Penulis (70)

M

M. Gerstung

C

Clemency Jolly

I

I. Leshchiner

S

S. Dentro

S

Santiago Gonzalez

T

T. Mitchell

Y

Yulia Rubanova

P

Pavana Anur

K

K. Yu

M

M. Tarabichi

A

A. Deshwar

J

J. Wintersinger

K

K. Kleinheinz

I

I. Vázquez-García

K

K. Haase

L

L. Jerman

S

Subhajit Sengupta

G

G. Macintyre

S

S. Malikić

N

Nilgun Donmez

D

D. Livitz

M

Marek Cmero

J

J. Demeulemeester

S

S. Schumacher

Y

Yu Fan

X

Xiaotong Yao

J

Juhee Lee

M

M. Schlesner

P

P. Boutros

D

D. Bowtell

H

Hongtu Zhu

G

G. Getz

M

M. Imieliński

R

R. Beroukhim

S

S. C. Sahinalp

Y

Yuan Ji

M

M. Peifer

F

F. Markowetz

V

Ville Mustonen

K

Ke Yuan

W

Wenyi Wang

Q

Q. Morris

D

D. J. Adams

P

Peter J. Campbell

S

S. Cao

E

E. Christie

Y

Yupeng Cun

K

K. Dawson

R

Ruben M. Drews

R

R. Eils

M

M. Fittall

D

D. Garsed

G

G. Ha

H

H. Lee-Six

I

I. Martincorena

L

Layla Oesper

M

Myron Peto

B

Benjamin J. Raphael

D

D. Rosebrock

A

A. Salcedo

R

Ruian Shi

S

S. Shin

O

O. Spiro

L

Lincoln Stein

S

Shankar Vembu

D

David A. Wheeler

T

Tsun-Po Yang

P

P. Spellman

D

D. Wedge

P

P. Loo

Format Sitasi

APA MLA BibTeX
Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S., Gonzalez, S., Mitchell, T. et al. (2017). The evolutionary history of 2,658 cancers. https://doi.org/10.1038/s41586-019-1907-7

Akses Cepat

Lihat di Sumber doi.org/10.1038/s41586-019-1907-7
Informasi Jurnal
Tahun Terbit
2017
Bahasa
en
Total Sitasi
918×
Sumber Database
Semantic Scholar
DOI
10.1038/s41586-019-1907-7
Akses
Open Access ✓