A 1-kb Alu-mediated germ-line deletion removing BRCA1 exon 17.
Although more than 100 different BRCA1 germ-line mutations have already been identified in breast and/or ovarian cancer families, we report for the first time a deleterious genomic rearrangement in BRCA1. A 1-kb deletion comprising exon 17 was found in a large breast and ovarian cancer family, leading to a frameshift in the mutant mRNA due to the absence of exon 17. This deletion is probably the result of a recombination between two closely related Alu sequences. It was not detected by conventional PCR-based methods involving the genomic screening of the 22 coding exons or reverse transcription-PCR because the transcript without exon 17 is unstable in lymphoblastoid cell lines. Therefore, rearrangements in the BRCA1 gene should be sought in breast/ovarian cancer families in which no mutations have been found by PCR-based methods in the coding region or in the splice sites.
Puget
N
N
IARC, Lyon, France.
Torchard
D
D
Serova-Sinilnikova
O M
OM
Lynch
H T
HT
Feunteun
J
J
Lenoir
G M
GM
Mazoyer
S
S
D019313:BRCA1 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion
D019313:BRCA1 Protein