Patterns of allele losses suggest the existence of five distinct regions of LOH on chromosome 17 in breast cancer.
Chromosome 17 is a frequent target during breast-cancer formation and progression. It has been shown to be affected by allele losses at multiple sites, as well as by DNA amplification. Our aim was to delineate a map of the genetic alterations on chromosome 17 in a given set of breast tumors. To this end we analyzed 151 pairs of tumor and cognate lymphocyte DNAs by Southern blotting with 5 RFLP or VNTR probes and by PCR at 8 CA repeat polymorphic loci for LOHs. Moreover, we studied DNA amplification of the evi2, erbB2, thraI, gcsf and rara genes. Data presented here point strongly to the existence of 5 distinct regions of allele losses on chromosome 17:2 on 17p, 3 on 17q. Of the 2 regions on 17p, one involves tp53 while the second is located more distally toward the telomere. LOH was found in 45.9% and 58.8% respectively. The 3 regions on 17q are located: (i) on the proximal portion of the long arm band q21, corresponding to the brcaI region; (ii) in a central region defined by the marker D17S74; (iii) on the distal part of 17q (band q25) characterized by losses of the marker D17S24. Each of these regions presented respectively allele losses in 47.5%, 33.3% and 40.8% of the informative tumors. Whereas some tumors presented patterns of LOH consistent with the loss of a complete chromosomal arm or of large portions of the chromosome, a high proportion of the analyzed tumors showed interstitial losses. Amplifications were found in 15% of the tumors and were centered around erbB2.(ABSTRACT TRUNCATED AT 250 WORDS)
Kirchweger
R
R
Erste Frauenklinik, Allgemeines Krankenhaus, Vienna, Austria.
Zeillinger
R
R
Schneeberger
C
C
Speiser
P
P
Louason
G
G
Theillet
C
C
D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000502:physiology*; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D017353:Gene Deletion; D014644:Genetic Variation; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid
D015342:DNA Probes; D004273:DNA, Neoplasm; D004274:DNA, Recombinant