title: Identification of novel large genomic rearrangements at the BRCA1 locus in Malaysian women with breast cancer.
abstract: BACKGROUND
  The incidence of breast cancer has been on the rise in Malaysia. It is suggested that a subset of breast cancer cases were associated with germline mutation in breast cancer susceptibility (BRCA) genes. Most of the BRCA mutations reported in Malaysia were point mutations, small deletions and insertions. Here we report the first study of BRCA large genomic rearrangements (LGRs) in Malaysia. We aimed to detect the presence of LGRs in the BRCA genes of Malaysian patients with breast cancer.
  
  
  METHODS
  Multiplex ligation-dependent probe amplification (MLPA) for BRCA LGRs was carried out on 100 patients (60 were high-risk breast cancer patients previously tested negative/positive for BRCA1 and BRCA2 mutations, and 40 were sporadic breast cancer patients), recruited from three major referral centres, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ).
  
  
  RESULTS
  Two novel BRCA1 rearrangements were detected in patients with sporadic breast cancer; both results were confirmed by quantitative PCR. No LGRs were found in patients with high-risk breast cancer. The two large genomic rearrangements detected were genomic amplifications of exon 3 and exon 10. No BRCA2 genomic rearrangement was found in both high-risk and sporadic breast cancer patients.
  
  
  CONCLUSIONS
  These results will be helpful to understand the mutation spectrum of BRCA1 and BRCA2 genes in Malaysian patients with breast cancer. Further studies involving larger samples are required to establish a genetic screening strategy for both high-risk and sporadic breast cancer patients.
authors.affiliation: Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia. sharifah@ppukm.ukm.my
authors.forename: Noor Akmal
authors.initials: NA
authors.lastname: Sharifah
authors.forename: Md Isa
authors.initials: MI
authors.lastname: Nurismah
authors.forename: Han Chung
authors.initials: HC
authors.lastname: Lee
authors.forename: Aziz Nur
authors.initials: AN
authors.lastname: Aisyah
authors.forename: Ching Huat
authors.initials: CH
authors.lastname: Clarence-Ko
authors.forename: Ismail
authors.initials: I
authors.lastname: Naqiyah
authors.forename: Mohamad
authors.initials: M
authors.lastname: Rohaizak
authors.forename: Ismail
authors.initials: I
authors.lastname: Fuad
authors.forename: A Rahman
authors.initials: AR
authors.lastname: A Jamal
authors.forename: Abdul Latiff
authors.initials: AL
authors.lastname: Zarina
authors.forename: Emran
authors.initials: E
authors.lastname: Nor Aina
authors.forename: Kitan
authors.initials: K
authors.lastname: Normayah
authors.forename: Abdullah
authors.initials: A
authors.lastname: Nor Hisham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D005820:Genetic Testing; D015894:Genome, Human; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004273:DNA, Neoplasm