Germline DNA copy number variation in familial and early-onset breast cancer.
BACKGROUND
Genetic factors predisposing individuals to cancer remain elusive in the majority of patients with a familial or clinical history suggestive of hereditary breast cancer. Germline DNA copy number variation (CNV) has recently been implicated in predisposition to cancers such as neuroblastomas as well as prostate and colorectal cancer. We evaluated the role of germline CNVs in breast cancer susceptibility, in particular those with low population frequencies (rare CNVs), which are more likely to cause disease."


METHODS
Using whole-genome comparative genomic hybridization on microarrays, we screened a cohort of women fulfilling criteria for hereditary breast cancer who did not carry BRCA1/BRCA2 mutations.


RESULTS
The median numbers of total and rare CNVs per genome were not different between controls and patients. A total of 26 rare germline CNVs were identified in 68 cancer patients, however, a proportion that was significantly different (P = 0.0311) from the control group (23 rare CNVs in 100 individuals). Several of the genes affected by CNV in patients and controls had already been implicated in cancer.


CONCLUSIONS
This study is the first to explore the contribution of germline CNVs to BRCA1/2-negative familial and early-onset breast cancer. The data suggest that rare CNVs may contribute to cancer predisposition in this small cohort of patients, and this trend needs to be confirmed in larger population samples.
National Institute of Science and Technology in Oncogenomics, AC Camargo Hospital, Rua Taguá 440, 01508-010, São Paulo, Brazil. ana.krepischi@gmail.com
Ana Cv
AC
Krepischi
Maria Isabel W
MI
Achatz
Erika Mm
EM
Santos
Silvia S
SS
Costa
Bianca Cg
BC
Lisboa
Helena
H
Brentani
Tiago M
TM
Santos
Amanda
A
Gonçalves
Amanda F
AF
Nóbrega
Peter L
PL
Pearson
Angela M
AM
Vianna-Morgante
Dirce M
DM
Carraro
Ricardo R
RR
Brentani
Carla
C
Rosenberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D018095:Germ-Line Mutation; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018709:Statistics, Nonparametric; D055815:Young Adult