Subtypes of familial breast tumours revealed by expression and copy number profiling.
Extensive expression profiling studies have shown that sporadic breast cancer is composed of five clinically relevant molecular subtypes. However, although BRCA1-related tumours are known to be predominantly basal-like, there are few published data on other classes of familial breast tumours. We analysed a cohort of 75 BRCA1, BRCA2 and non-BRCA1/2 breast tumours by gene expression profiling and found that 74% BRCA1 tumours were basal-like, 73% of BRCA2 tumours were luminal A or B, and 52% non-BRCA1/2 tumours were luminal A. Thirty-four tumours were also analysed by single nucleotide polymorphism-comparative genomic hybridization (SNP-CGH) arrays. Copy number data could predict whether a tumour was basal-like or luminal with high accuracy, but could not predict its mutation class. Basal-like BRCA1 and basal-like non-BRCA1 tumours were very similar, and contained the highest number of chromosome aberrations. We identified regions of frequent gain containing potential driver genes in the basal (8q and 12p) and luminal A tumours (1q and 17q). Regions of homozygous loss associated with decreased expression of potential tumour suppressor genes were also detected, including in basal tumours (5q and 9p), and basal and luminal tumours (10q). This study highlights the heterogeneity of familial tumours and the clinical consequences for treatment and prognosis.
Waddell
Nic
N
Queensland Institute of Medical Research, Brisbane, Australia.
Arnold
Jeremy
J
Cocciardi
Sibylle
S
da Silva
Leonard
L
Marsh
Anna
A
Riley
Joan
J
Johnstone
Cameron N
CN
Orloff
Mohammed
M
Assie
Guillaume
G
Eng
Charis
C
Reid
Lynne
L
Keith
Patricia
P
Yan
Max
M
Fox
Stephen
S
Devilee
Peter
P
Godwin
Andrew K
AK
Hogervorst
Frans B L
FB
Couch
Fergus
F
Grimmond
Sean
S
Flanagan
James M
JM
Khanna
Kumkum
K
Simpson
Peter T
PT
Lakhani
Sunil R
SR
Chenevix-Trench
Georgia
G
D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D019656:Loss of Heterozygosity; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human