Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers.
Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer.
Sanger sequencing has been the gold standard in identifying these mutations. However,
4–28% of inherited BRCA mutations may be due to large genomic rearrangements (LGRs), which could be missed
by using Sanger sequencing alone. Our aim is to evaluate the pick-up rate of LGRs
in our cohort. A total of 1,236 clinically high-risk patients with breast and/or ovarian
cancers were recruited through The Hong Kong Hereditary Breast Cancer Family Registry
from 2007 to 2014. Full gene sequencing (either Sanger or next generation sequencing)
and multiplex ligation-dependent probe amplification (MLPA) were performed. We identified
120 deleterious BRCA mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated approach, both small nucleotide variations and
LGRs could be detected. We suggest that MLPA should be incorporated into the standard
practice for genetic testing to avoid false-negative results, which would greatly
affect the management of these high-risk families.
Keywords
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Article info
Publication history
Published online: June 09, 2015
Accepted:
May 12,
2015
Received in revised form:
May 11,
2015
Received:
March 20,
2015
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
