title: Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer.
abstract: Large genomic rearrangements have been reported to account for about 10-15% of BRCA1 gene mutations. Approximately, 90 BRCA rearrangements have been described to date, all of which but one have been reported in Caucasian populations of predominantly Western European descent. Knowledge of BRCA genomic rearrangements in Asian populations is still largely unknown. In this study, we have investigated for the presence of BRCA rearrangements among Asian patients with early onset or familial history of breast or ovarian cancer. Using multiplex ligation-dependent probe amplification (MLPA), we have analyzed 100 Singapore patients who previously tested negative for deleterious BRCA mutations by the conventional polymerase chain reaction-based mutation detection methods. Three novel BRCA rearrangements were detected, two of which were characterized. The patients with the rearrangements, a BRCA1 exon 13 duplication, a BRCA1 exon 13-15 deletion and a BRCA2 exon 4-11 duplication, comprise 3% of those previously tested negative for BRCA mutations. Of the BRCA1 and BRCA2 pathogenic mutations identified in our studies on Asian high-risk breast and ovarian patients with cancer to date, these rearrangements constitute 2/19 and 1/2 of the BRCA1 and BRCA2 pathogenic mutations, respectively. Given the increasing number of rearrangements reported in recent years and their contribution to the BRCA mutation spectrum, the presence of BRCA large exon rearrangements in Asian populations should be investigated where clinical, diagnostic service is recommended.
authors.affiliation: Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Y K
authors.initials: YK
authors.lastname: Lim
authors.forename: P T C
authors.initials: PT
authors.lastname: Lau
authors.forename: A B
authors.initials: AB
authors.lastname: Ali
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.forename: J E-L
authors.initials: JE
authors.lastname: Wong
authors.forename: T C
authors.initials: TC
authors.lastname: Putti
authors.forename: J-H
authors.initials: JH
authors.lastname: Sng
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques; D010051:Ovarian Neoplasms / Q000235:genetics*; D017384:Sequence Deletion; D012846:Singapore
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm