Complex landscapes of somatic rearrangement in human breast cancer genomes.
Multiple somatic rearrangements are often found in cancer genomes; however, the underlying processes of rearrangement and their contribution to cancer development are poorly characterized. Here we use a paired-end sequencing strategy to identify somatic rearrangements in breast cancer genomes. There are more rearrangements in some breast cancers than previously appreciated. Rearrangements are more frequent over gene footprints and most are intrachromosomal. Multiple rearrangement architectures are present, but tandem duplications are particularly common in some cancers, perhaps reflecting a specific defect in DNA maintenance. Short overlapping sequences at most rearrangement junctions indicate that these have been mediated by non-homologous end-joining DNA repair, although varying sequence patterns indicate that multiple processes of this type are operative. Several expressed in-frame fusion genes were identified but none was recurrent. The study provides a new perspective on cancer genomes, highlighting the diversity of somatic rearrangements and their potential contribution to cancer development.
Stephens
Philip J
PJ
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
McBride
David J
DJ
Lin
Meng-Lay
ML
Varela
Ignacio
I
Pleasance
Erin D
ED
Simpson
Jared T
JT
Stebbings
Lucy A
LA
Leroy
Catherine
C
Edkins
Sarah
S
Mudie
Laura J
LJ
Greenman
Chris D
CD
Jia
Mingming
M
Latimer
Calli
C
Teague
Jon W
JW
Lau
King Wai
KW
Burton
John
J
Quail
Michael A
MA
Swerdlow
Harold
H
Churcher
Carol
C
Natrajan
Rachael
R
Sieuwerts
Anieta M
AM
Martens
John W M
JW
Silver
Daniel P
DP
Langerød
Anita
A
Russnes
Hege E G
HE
Foekens
John A
JA
Reis-Filho
Jorge S
JS
van 't Veer
Laura
L
Richardson
Andrea L
AL
Børresen-Dale
Anne-Lise
AL
Campbell
Peter J
PJ
Futreal
P Andrew
PA
Stratton
Michael R
MR
D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D053960:DNA Breaks; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D015698:Genomic Library; D006801:Humans; D017422:Sequence Analysis, DNA