Genomic rearrangement screening of theBRCA1from seventy Iranian high-risk breast cancer families.
BACKGROUND
The second leading cause of cancer deaths in women is breast cancer. Germline mutations in susceptibility breast cancer geneBRCA1increase the lifetime risk of breast cancer. Eighty-one large genomic rearrangements (LGRs) have been reported up to date inBRCA1gene, and evaluation of these rearrangements helps with precise risk assessment in high-risk individuals. In this study, we have investigated LGRs inBRCA1among Iranian high-risk breast cancer families.


METHODS
Seventy patients with breast cancer who were identified negative for point mutations or small deletions/insertions ofBRCA1gene were selected. Deletions and duplications ofBRCA1gene were evaluated using multiplex ligation-dependent probe amplification (MLPA).


RESULTS
Two deletions, deletion of exons 1A/1B-2 and exon 24, were detected in two patients with breast cancer. The former alteration was found in a woman with a strong family history of breast cancer while the latter one was detected in a woman with early onset of breast cancer.


CONCLUSIONS
Although our data confirm that LGRs inBRCA1comprise a relatively small proportion of mutations in hereditary breast cancer in the Iranian population, MLPA analysis might be considered for screening of LGRs in high-risk individuals. It is worth to note that our results are consistent with previous studies in various Asian and European countries.
Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
Maryam
M
Sedghi
Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Elham
E
Esfandiari
Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Esmat
E
Fazel-Najafabadi
Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Division of Genetics and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.
Mansoor
M
Salehi
Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Abbas
A
Salavaty
Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Shirin
S
Fattahpour
Department of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Isfahan Neurosciences Research Center, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
Leila
L
Dehghani
Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
Nayerossadat
N
Nouri
Department of Oncology, Isfahan University of Medical Sciences, Isfahan, Iran.
Fariborz
F
Mokarian
BRCA1 gene; breast cancer; large genomic rearrangements; multiplex ligation-dependent probe amplification