Landscape of somatic mutations in 560 breast cancer whole-genome sequences - Archive ouverte HAL Access content directly
Journal Articles Nature Year : 2016

Landscape of somatic mutations in 560 breast cancer whole-genome sequences

(1) , (1) , (2) , (1) , (1) , (1) , (1) , (1) , (1) , (1) , (1) , (1) , (3) , (4) , (1) , (5) , (6) , (5) , (2) , (7) , (8) , (9) , (10) , (1) , (11) , (12) , (1) , (13) , (3) , (1) , (14) , (15) , (16, 1) , (17) , (18) , (19) , (15) , (20) , (1) , (1) , (1) , (1) , (1) , (21) , (22) , (23) , (1) , (1) , (3, 24, 25) , (26) , (27, 28) , (29) , (1) , (1) , (30) , (1) , (31) , (32) , (33) , (34) , (35, 36) , (1) , (37) , (38, 39) , (40) , (41) , (42) , (43) , (2) , (44, 45) , (46) , (47, 48) , (1) , (1) , (49, 50) , (51, 52) , (29) , (30) , (53) , (1) , (54) , (14) , (3) , (5) , (55) , (56) , (57) , (1)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
Sandrine Boyault
  • Function : Author
  • PersonId : 757688
  • IdRef : 075706466
Se Jin Jang
  • Function : Author
Hee Jin Lee
  • Function : Author
Carlos Caldas
Åke Borg
  • Function : Author
Christos Sotiriou

Abstract

We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
Fichier principal
Vignette du fichier
emss-68344.pdf (4.91 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

hal-01388447 , version 1 (12-07-2017)

Identifiers

Cite

Serena Nik-Zainal, Helen R. Davies, Johan Staaf, Manasa Ramakrishna, Dominik Glodzik, et al.. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature, 2016, 534 (7605), pp.47 - 54. ⟨10.1038/nature17676⟩. ⟨hal-01388447⟩
474 View
779 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More