Loss of heterozygosity and amplification on chromosome 11q in human ovarian cancer.
The 11q13 chromosomal region encodes oncogenes relevant to a variety of human cancers as well as a tumour suppressor gene implicated in multiple endocrine neoplasia type 1. In addition, high affinity folate receptor (FOLR1), which maps to 11q13.3-13.5, is expressed at an elevated level on the surface of over 80% of nonmucinous epithelial ovarian cancers. Further telomeric, 11q breakpoints are found in many cancers. We studied the involvement of 11q markers in ovarian cancer by looking for tumour-specific loss of heterozygosity (LOH), as well as amplification or rearrangements that might explain the overexpression of FOLR1. Twenty eight epithelial ovarian cancers, along with lymphocyte DNA from the same individual were used for Southern blotting with polymorphic probes from 11q. PCR primers from 11q23.3 were also used. The 11q13 band was amplified in four out of 28 cancers. The amplicon included the probe D11S146 as well as FGF3 (formerly INT2) and FOLR1 in one out of these four cases, thus crossing the bcl1 translocation breakpoint. LOH was seen in three out of 16 cases with FGF3 (11q13). A much higher frequency of LOH (8/12) was found at 11q23.3-qter, implying the presence of a tumour suppressor gene in this region.
Foulkes
W D
WD
Human Immunogenetics Laboratory, Imperial Cancer Research Fund, London, UK.
Campbell
I G
IG
Stamp
G W
GW
Trowsdale
J
J
D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000502:physiology*; D015342:DNA Probes; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000502:physiology
D015342:DNA Probes