A 400 kb novel deletion unit centromeric to the BRCA1 gene in sporadic epithelial ovarian cancer.
Allelic deletions on chromosome 17q21 in sporadic ovarian cancer are common, suggesting that inactivation of a tumor suppressor gene(s) in that region may be important for the etiology of these tumors. The recently identified BRCA1 gene on 17q21, involved in the development of familial breast/ovarian cancer, could be a candidate. However, inactivating mutations on BRCA1 in sporadic ovarian cancer has been rarely described. Furthermore, the potential relationship of BRCA1 gene to ovarian tumors of borderline malignancy remains also unclear. We constructed a highly detailed deletion map of chromosome 17q21 based on PCR amplification of eight polymorphic tandem repeat markers in a 650 kb area including three BRCA1 intragenic markers. DNA from 52 sporadic ovarian cancers and 26 borderline tumors, together with their corresponding normal control tissues were used. Only one borderline tumor showed loss of heterozygosity at one marker, whereas 65% of invasive ovarian cancers displayed allelic loss in at least one of the markers studied. A common deletion unit, located approximately 60kb centromeric to BRCA1, was revealed. These results suggest that inactivation of the BRCA1 gene may not be responsible for the development of borderline ovarian tumors and that another tumor suppressor gene, located centromeric to the BRCA1 gene, may play a role in sporadic ovarian cancer development.
Tangir
J
J
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Muto
M G
MG
Berkowitz
R S
RS
Welch
W R
WR
Bell
D A
DA
Mok
S C
SC
D000483:Alleles; D019313:BRCA1 Protein; D001943:Breast Neoplasms / Q000235:genetics; D002503:Centromere; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D019313:BRCA1 Protein; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors