High-resolution integrated map encompassing the breast cancer loss of heterozygosity region on human chromosome 16q22.1.
Loss of heterozygosity (LOH) on the long arm of human chromosome 16 is a common genetic alteration observed in both invasive ductal and invasive lobular breast carcinomas. We have generated a high-resolution integrated map encompassing the smallest region of LOH overlap within chromosome 16q22.1 (SRO2). Southern hybridization experiments using more than 140 probes resulted in the assembly of 152 bacterial large-insert clones into a 2.8-Mb contig covering SRO2. The structure of the contig was verified by long-range mapping using total human genomic DNA, and the contig orientation was determined by fluorescence in situ hybridization. A total of 68 transcripts have been identified in the map. One of the genes residing within SRO2 is the E-cadherin gene, CDH1, which has previously been shown to be mutated in lobular breast carcinomas, resulting in loss of E-cadherin expression. In most cases of ductal carcinoma, which is the major mammary cancer type, E-cadherin is normally expressed, suggesting that other genes within 16q22.1 are involved in the development of this tumor subtype. The high-resolution map presented in this study provides a valuable resource for identification of tumor suppressor genes expected to be involved in the etiology of breast carcinomas.
Frengen
E
E
The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
Rocca-Serra
P
P
Shaposhnikov
S
S
Taine
L
L
Thorsen
J
J
Bepoldin
C
C
Krekling
M
M
Lafon
D
D
Aas
K K
KK
El Monéim
A A
AA
Johansen
H
H
Longy
M
M
Prydz
H
H
Dorion-Bonnet
F
F
D001943:Breast Neoplasms / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D020161:Physical Chromosome Mapping; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping
D005819:Genetic Markers